Anti-inflammatory (halo-4-biphenylyl)-alkanolamines

ABSTRACT

Compounds of the formula 
     
         R--A--Z 
    
     wherein R is 4-biphenylyl or 4-phenoxyphenyl or a corresponding group monosubstituted or polysubstituted by one or more of F, Cl and Br; A is --CH(CH 3 )--CH 2  --(CH 2 ) n  --, --C(CH 3 )═CH--(CH 2 ) n  -- or --C(OH) (CH 3 )--CH 2  --(CH 2 ) n  --; Z is --NR 1  R 2 , imidazol-1-yl, phthalimido or 4,5-dihydro-4-oxophthalazin-1-yl-amino; R 1  and R 2  each are H or alkyl, azaalkyl or acyl, each of 1 - 6 carbon atoms or, collectively, are alkylene of 4 - 7 carbon atoms, 3-oxapentamethylene or 3-R 3  -3-azapentamethylene; R 3  is H or alkyl or hydroxyalkyl each of up to 6 carbon atoms; and n is 0, 1 or 2, and their physiologically acceptable acid addition salts possess anti-inflammatory, anti-arteriosclerotic and serum cholesterol and triglyceride level lowering activities.

BACKGROUND OF THE INVENTION

This invention relates to novel araliphatic nitrogen compounds.

SUMMARY OF THE INVENTION

In a composition aspect, this invention relates to compounds of thegeneral formula I.

    r--a--z                                                    i

wherein R is a 4-biphenylyl or 4-phenoxyphenyl or a corresponding groupmonosubsituted or polysubstituted by one or more of F, Cl and Br; A is--CH(CH₃)--CH₂ --(CH₂)_(n) --,--C(CH₃)═CH--(CH₂)_(n) -- or--C(OH)--(CH₃)--CH₂ --(CH₂)_(n) --, Z is --NR¹ R², imidazol-1-yl,phthalimido or 4,5-dihydro-4-oxophthalazin-1-yl-amino; R¹ and R² eachare H or alkyl, azaalkyl or acyl, each of 1 - 6 carbon atoms orcollectively are alkylene of 4 - 7 carbon atoms, 3-oxapentamethylene or3-R³ -3-azapentamethylene; R³ is H or alkyl or hydroxyalkyl each of upto 6 carbon atoms; and n is 0, 1 or 2, and their physiologicallyacceptable acid addition salts.

In another composition aspect, this invention relates to pharmaceuticalcompositions, comprising, in unit dosage form, a novel compound of thisinvention in admixture with a pharmaceutically acceptable carrier.

In process aspects, this invention relates to processes for theproduction and use of the novel compounds of this invention.

DETAILED DISCUSSION

In the compounds of Formula I, R is preferably unsubstituted4-biphenylyl or 4-phenoxyphenyl radical or monosubstituted 4-biphenylylor 4-phenoxyphenyl.

Of the biphenylyl substituents, most preferred is F followed by Cl. Thesubstituents are most preferably in the 4'-position, for example,4'-fluoro-4-biphenylyl, 4'-chloro-4-biphenylyl and4'-bromo-4-biphenylyl, but the 2'-position is also preferred, forexample, 2'-fluoro-4-biphenylyl, 2'-chloro-4-biphenylyl and2'-bromo-4-biphenylyl. However, the biphenylyl radical can also besubstituted in the 2-, 3- and/or 3'-position. Of the polysubstitutedbiphenylyl radicals, those which are disubstituted, particularly thosedisubstituted in the 2', 4'-position, are preferred, however,3-,4-,5-,6-,7-,8- and 9-fold substitution of the biphenylyl radical isalso possible. Of the polysubstituted biphenylyl radicals, those whosesubstituents are identical are preferred, for example,difluoro-4-biphenylyl, e.g., 2', 4'-difluoro-4-biphenylyl,dichloro-4-biphenylyl, e.g., 2',4'-dichloro-4-biphenylyl, anddibromo-4-biphenylyl, e.g., 2',4'-dibromo-4-biphenylyl. Preferred amongthe biphenylyl radicals bearing different substituents are those havingat least one fluorine atom, for example,2'-fluoro-4'-chloro-4-biphenylyl, 2'-fluoro-4'-bromo-4-biphenylyl,2'-chloro-4'-fluoro-4-biphenylyl and 2'-bromo-4'-fluoro-4-biphenylyl.Preferred among the polysubstituted biphenylyl radicals are thefluorine-substituted biphenylyl radicals, for example,nonafluoro-4-biphenylyl.

Of the substituents on the 4-phenoxyphenyl radical, Cl is preferred. Thesubstituents on the 4-phenoxyphenyl radical are preferably on thephenoxy group, particularly at the p-position, but also at theo-position. Examples of preferred substituted 4-phenoxyphenyl radicalsare 4 -p-chlorophenoxyphenyl, 4-o-chlorophenoxyphenyl,4-p-fluorophenoxyphenyl and 4-p-bromophenoxyphenyl. The phenoxy groupcan also be substituted at the m-position. The phenyl radical (which issubstituted in the 4-position by the phenoxy group) can be substitutedat the 2-, 2-, 5- and/or 6-position by F, Cl and/or Br. Preferred of thepolysubstituted 4-phenoxyphenyl radicals are those which aredisubstituted, particularly those which are substituted in the 2- and4-position of the phenoxy group. However, 3-, 4-, 5-, 6-, 7-, 8-, or9-fold substitution of the 4-phenoxyphenyl radical is also possible.Preferred of the polysubstituted 4-phenoxyphenyl radicals are thosesubstituents which are identical, for example,4-(2,4-difluorophenoxy)-phenyl, 4-(2,4-dichlorophenoxy)phenyl,4-(2,4-dibromophenoxy)-phenyl and 4-(pentafluorophenoxy)phenyl.

In the compounds of Formula I, n is preferably 1, i.e., the radical Apreferably has 4 carbon atoms. The radical A is preferably--CH(CH₃)--CH₂ --(CH₂)_(n) -- or --C(OH)(CH₃)--CH₂ (CH₂)_(n) --,particularly --CH(CH₃)--CH₂ --CH₂ -- or --C(OH)(CH₃)--CH₂ --CH₂ --, andalso, for example, --C(CH₃)═CH--CH₂ --, --CH(CH₃)--CH₂ --,--C(OH)(CH₃)--CH₂ --, --CH(CH₃)--(CH₂)₃ --, --C(OH)(CH₃)--(CH₂)₃ -- or--C(CH₃)═CH(CH₂)₂ --.

When R¹ and/or R² are alkyl, alkyl is preferably methyl, ethyl, n-propylor isopropyl, but also can be, for example, n-butyl, isobutyl,sec.-butyl, tert.-butyl, 1-pentyl, 2-pentyl, 3-pentyl, 2-methyl-1-butyl,2-methyl-2-butyl, 3-methyl-1-butyl (isoamyl), 3-methyl-2-butyl,2,2-dimethyl-1-propyl (neopentyl), 1-hexyl or 4-methyl-1-pentyl. When R¹is alkyl, R² is preferably H or the same alkyl group. Azaalkyl can be R¹R² N-alkyl and is preferably dialkylaminoalkyl, which is preferablybranched and more preferably is dimethylaminoethyl, such as2-dimethylaminoethyl, diethylaminoethyl, such as 2-diethylaminoethyl ordiemthylaminopropyl, such as 2- or 3-dimethylaminopropyl. Acyl ispreferably alkanoyl, and more preferably acetyl, but can also be, forexample, formyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl,trimethylacetyl, methylethylacetyl, caproyl, isocaproyl,tert.-butylacetyl, diethylacetyl and nicotinoyl. When R¹ is acyl, R² ispreferably H. Alkylene preferably is tetramethylene, 1- or2-methyltetramethylene, pentamethylene, 1-, 2- or3-methylpentamethylene, 1,5-dimethylpentamethylene or hexamethylene, butcan also be, for example, 1- or 2-ethyltetramethylene, 1- or2-n-propyltetramethylene, 1- or 2-isopropyltetramethylene, 1,2-, 1,3-,1,4-, or 2,3-dimethyltetramethylene, 1,3-, 1,3-, 1,4-, 2,3-, or2,4-dimethylpentamethylene, 1-, 2-, or 3-ethylpentamethylene and 1-, 2-,3-, or 4-methylhexamethylene. R³ is preferably H, methyl, ethyl or2-hydroxyethyl.

Accordingly, NR¹ R² is preferably amino, methylamino, ethylamino,n-propylamino, isopropylamino, dimethylamino, diethylamino,di-n-propylamino, diisopropylamino, 2-dimethylaminoethylamino,2-diethylaminoethylamino, 2- or 3-dimethylaminopropylamino, acetamido,pyrrolidino, piperidino, 2-, 3- or 4-methylpiperidino,2,6-dimethylpiperidino, homopiperidino, morpholino, piperazino,4-methylpiperazino, 4-ethylpiperazino or 4-(2-hydroxyethyl)-piperazino.

In preferred embodiments this invention relates to compounds of FormulaI wherein at least one of R, A and Z has one of the preferred valuesindicated above. Examples of such preferred groups of compounds arethose of Formula I wherein:

Ia : R is unsubstituted 4-biphenylyl or 4-biphenylyl monosubstituted orpolysubstituted by F, Cl and/or Br;

Ib: R is 4-phenoxyphenylyl or 4-phenoxyphenylyl monosubstituted orpolysubstituted by F, Cl and/or Br;

Ic: R is 4-biphenylyl, fluoro-4-biphenylyl, chloro-4-biphenylyl,bromo-4-biphenylyl, difluoro-4-biphenylyl, p-phenoxyphenyl,4-(chlorophenoxy)-phenyl or 4-(bromophenoxy)-phenyl;

Id: R is p-biphenylyl, 2'-fluoro-4-biphenylyl, 4'-fluoro-4-biphenylyl,4'-chloro-4-biphenylyl, 4'-bromo-4-biphenylyl,2',4'-difluoro-4-biphenylyl, 4-p-chlorophenoxy-phenyl or4-p-bromophenoxyphenyl;

Ie: R is p-biphenylyl, 4'-fluoro-4-biphenylyl, 4'-chloro-4-biphenylyl or4-p-chlorophenoxy-phenyl;

If: A is --CH(CH₃)--CH₂ CH₂ --, --C(OH)(CH.sub. 3)--CH₂ --(CH₂)_(n) --or --C(CH₃)═CH--CH₂ --;

Ig: A is --C(OH)(CH.sub. 3)--CH₂ --(CH₂)_(n) --;

Ih: A is --CH(CH₃)--CH₂ CH₂ -- or --C(OH)(CH.sub. 3)--CH₂ CH₂ --;

Ii: A is --C(OH)(CH.sub. 3)--CH₂ CH₂ --;

Ij: Z is amino, diethylamino, 2-diethylaminoethylamino, acetamido,piperidino, 4-methylpiperidino, morpholino,4-(2-hydroxyethyl)-piperazino, imidazol-1-yl, phthalimido or3,4-dihydro-4-oxo-phthalazin-1-ylamino;

Ik: Z is amino, diethylamino, acetamido, piperidino, morpholino,imidazol-1-yl or phthalimido;

Il: Z is amino;

Im: Z is morpholino;

In: Z is phthalimido;

Io: R is 4-biphenylyl or 4-biphenylyl monosubstituted or polysubstitutedby F, Cl and/or Br.,

A is (CH(CH₃)--(CH₂)₂ --, --C(CH₃)═CHCH₂ -- or --C(OH)(CH.sub.3)--(CH₂)₂ -- and

Z is amino;

Ip: R is p-biphenylyl, 2'-fluoro-4-biphenylyl, 4'-fluoro-4-biphenylyl,4'-chloro-4-biphenylyl, 4'-bromo-4-biphenylyl,2',4'-difluoro-4-biphenylyl, 4-p-chlorophenoxy-phenyl or4-p-bromophenoxy-phenyl,

A is --CH(CH₃)--(CH₂)₂ --, --C(OH)(CH.sub. 3)--CH₂ --(CH₂)_(n) -- or--C(CH₃)═CH--CH₂ --, and

Z is amino diethylamino, 2-diethylaminoethylamino, acetamido,piperidino, 4-methylpiperidino, morpholino,4-(2-hydroxyethyl)-piperazino, imidazol-1-yl, phthalimido or3,4-dihydro-4-oxo-phthalazin-1-yl-amino;

Iq: R is p-biphenylyl, 2'-fluoro-4-biphenylyl, 4'-fluoro-4-biphenylyl,4'-chloro-4-biphenylyl, 4'-bromo-4-biphenylyl or2',4'-difluoro-4-biphenylyl,

A is --CH(CH₃)--(CH₂)₂ --, --C(OH)(CH.sub. 3)--CH₂ --(CH₂)_(n) -- or--C(CH₃)═CH--CH₂ --, and

Z is amino, diethylamino, 2-diethylaminoethylamino, acetamido,piperidino, 4-methylpiperidino, morpholino,4-(2-hydroxyethyl)-piperazino, imidazol-1-yl, phthalimido or3,4-dihydro-4-oxo-phthalazin-1-yl-amino;

Ir: R is 4-p-chlorophenoxy-phenyl or 4-p-bromophenoxyphenyl,

A is --CH(CH₃)--(CH₂)₂ or --C(OH)(CH.sub. 3)--(CH₂)₂ --, and

Z is amino, piperidino, 4-methylpiperidino, morpholino or phthalimido;

Is: R is p-biphenylyl, 4'-fluoro-4-biphenylyl, 4'-chloro-4-biphenylyl or4-p-chlorophenoxy-phenyl,

A is --CH(CH₃)--(CH₂)₂ -- or --C(OH)(CH.sub. 3)--(CH₂)₂ --, and

Z is amino, diethylamino, acetamido, piperidino, morpholino,imidazol-1-yl or phthalimido;

It: R is p-biphenylyl, 4'-fluoro-4-biphenylyl, 4'-chloro-4-biphenylyl or4-p-chlorophenoxy-phenyl,

A is --CH(CH₃)--(CH₂)₂ -- or --C(OH)(CH.sub. 3)--(CH₂)₂ --, and

Z is amino.

In a process aspect, this invention relates to a process for thepreparation of the compounds of Formula I and their physiologicallyacceptable acid addition salts, which comprises

(a) treating a compound of the general formula II

    r--q                                                       ii

wherein Q is a radical which can be reduced to the group --A--Z, and R,A and Z have the values given above, with a reducing agent; or

(b) treating a compound which otherwise corresponds to the generalFormula I but wherein the amino group and/or the hydroxyl group ispresent in a functionally modified form, with a solvolyzing agent; or

(c) reacting a compound of the general Formula III

    r--e                                                       iii

wherein E is --C(CH₃ )(OH)--(CH₂)_(m) --CH═CH₂, --CH(CH₃)--(CH₂)_(m)--CH═CH₂ or --A--X, m is 0 or 1, X is Cl, Br, I, OH or OH which isfunctionally modified in a reactive manner, and R and A have the valuesgiven above, with a compound of the general formula H-Z or with areactive derivative of such a compound; or

(d) treating an amine of the general Formula IV

    r--a--n(ch.sub.2 ch.sub.2 oh)--ch.sub.2 ch.sub.2 x         iv

wherein R, A and X have the values given above, with an agent whichsplits off HX; or

(e) reacting an amine of the general Formula V

    r--a--n(ch.sub.2 ch.sub.2 x).sub.2                         v

wherein R, A and X have the values given above, with a compound of thegeneral Formula H₂ NR₃ ; or

(f) diazotizing a compound of the general Formula VI

    r.sup.4 --a--z                                             vi

wherein R⁴ is a 4-biphenylyl or 4-phenoxyphenyl monosubstituted orpolysubstituted by NH₂ and, if appropriate, additionally monosubstitutedor polysubstituted by F, Cl and/or Br, and A and Z have the values givenabove, and then treating the resulting diazonium salt with ahalogenating agent; or

(g) reacting a compound of the general Formula VII

    q.sup.1 --r.sup.5 --a--z                                   vii

or a salt thereof, with a compound of the general Formula VIII

    r.sup.6 --q.sup.2                                          viii

or with a salt thereof, wherein one of Q¹ and Q² is OH and the other isX, R⁵ is p-phenylene or p-phenylene monosubstituted or polysubstitutedby F, Cl and/or Br, R⁶ is phenyl or phenyl which is monosubstituted orpolysubstituted by F, Cl and/or Br, and A, Z and X have the values givenabove, and, if appropriate, a thus-produced hydroxy compound of FormulaI [A═--C(OH)(CH.sub. 3)--CH₂ --(CH₂)_(n) -] is treated with adehydrating agent, and/or a thus-produced compound of Formula I [A ═--C(OH)(CH.sub. 3)--CH₂ --(CH₂)_(n) -- or --C(CH₃)═CH--(CH₂)_(n) --], istreated with a reducing agent, and/or in a thus-produced compound ofFormula I one or more chlorine atoms or bromine atoms are introduced bytreatment with chlorinating or brominating agents, and/or in athus-produced compound of Formula I radical Z is converted into anotherZ radical by treatment with an alkylating, acylating, solvolyzing and/orreducing agent, and/or a thus-produced free base of Formula I isconverted into a physiologically acceptable acid addition salt thereofby treatment with an acid.

In other respects the preparation of the compounds of Formula I iscarried out in accordance with methods which are in themselves known,such as are described in the literature (for example, in the standardworks such as Houben-Weyl, Methoden der organischen Chemie ("Methods ofOrganic Chemistry"), Georg-ThiemeVerlag, Stuttgart), and under thereaction conditions which are known and suitable for the reactionsmentioned. In the course thereof, it is also possible to make use ofvariants which are in themselves known and are not mentioned here ingreater detail.

In all the general formulae in the preceding and following text, R, Aand Z have the values given for Formula I unless otherwise expresslyindicated.

The starting compounds for the preparation of the compounds of Formula Iare, in part, known. They can be prepared by processes which are inthemselves known. If desired, the starting compounds can also be formedin situ and are not isolated from the reaction mixture but areimmediately reacted further to give a compound of Formula I.

In the compounds of Formula II, the radical Q is preferably the group--A¹ --Y wherein A¹ is --CH(CH₃)--(CH₂)_(n) --, --C(CH₃)═CH--(CH₂)_(m)-- or --C(OH)(CH.sub. 3)--(CH₂)_(n) --, m is 0 or 1, and Y is CN, CONR¹R², CH₂ NO₂, CH₂ N₃, CH₂ NR¹ --W (wherein W is a benzyl group or anotherradical which can be split off by hydrogenolysis), CH₂ N(W)₂, CH═NOH,CHOH--NR¹ R², CH═NR¹ CH₂ NR⁷ (wherein R⁷ is alkylidene or azaalkylidenein each case of 1 - 6 carbon atoms, oxo-alkylene of 4 - 7 carbon atoms,oxo-3-oxapentamethylene or oxo-3-R³ -3-azapentamethylene) or anotherradical which can be reduced to give a CH₂ --NR¹ R² group. In addition,the group Q can, for example, be -- C(═CH₂)--(CH₂)_(n+1) --Z,--C(═CH₂)--(CH₂)_(n) --Y, --CH(CH₃)--CH═CH--Z, --CH(CH₃)--CH═CH--Y,--C(OH)(CH.sub. 3)--CH═CH--Z, --C(OH)(CH.sub. 3)--CH═CH--Y,--C(═CH₂)--CH═CH--Z or --C(═CH₂)--CH═CH--Y.

The starting compounds of Formula II are, in general, new. They can,however, be prepared analogously to known processes. Thus, the acidamides of the formula R--C(OH)(CH.sub. 3)--(CH₂)_(p) --CONR¹ R² (p = 1or 2) can be obtained, for example, by Friedel-Crafts acetylation of thebiphenyls or diphenyl ethers of the formula R-H to give the ketones ofthe formula R-COCH₃, a Reformatsky reaction to give the hydroxy-estersof the formula R--C(OH)(CH.sub. 3)--(CH₂)_(p) --COOC₂ H₅ and reactionwith a compound of the formula HNR¹ R². Elimination of water leads tothe unsaturated amides of the formula R--C(CH₃)═CH--(CH₂)_(m) --CONR¹ R²and reduction leads to the saturated amides of the formulaR--CH(CH₃)--(CH₂)_(p) --CONR¹ R². Reduction of the hydroxy-estersmentioned, using HI, gives with simultaneous saponification, acids ofthe formula R--CH(CH₃)--(CH₂)_(p) --COOH, which can be converted bymeans of LiAlH₄ into the corresponding alcohols of the formulaR--CH(CH₃)--(CH₂)_(p) --CH₂ OH. Alcohols of the formulaR--C(OH)(CH₃)--(CH₂)_(p) --CH₂ OH can be obtained by reducing theabovementioned hydroxy-esters with LiAlH₄, and alcohols of the formulaR--C(CH₃ )═CH--(CH₂)_(p) --OH can be obtained by dehydration andsubsequent reduction of the hydroxy-esters. Reacting the ketones of theformula R--CO--CH₃ with KCN gives the cyanohydrins of the formulaR--C(OH)(CH₃)--CN, which can be hydrolyzed to give the amides of theformula R--C(OH)(CH₃)--CONH₂ or the hydroxy acids of the formulaR--C(OH)(CH₃)--COOH. Reduction of the hydroxy acids by various methodsgives the acids of the formula R--CH(CH₃)--COOH, the glycols of theformula R--C(OH)(CH₃)--CH₂ OH and the alcohols of the formulaR--CH(CH₃)--CH₂ OH. From the alcohols mentioned, it is possible toprepare, in a conventional manner, for example using SOCl₂ or PBr₃, thecorresponding halides, which can be converted, using alkali metalnitrites, into the corresponding nitro compounds of the formula R--A¹--CH₂ NO₂, using alkali metal azides, into the azides of the formulaR--A¹ --CH₂ N₃, or using amines of the formula W--NH₂ (for example,benzylamine) or (W)₂ NH, into amines of the formula R--A¹ --CH₂ --NH--Wor R--A¹ --CH₂ N(W)₂. Oxidation of the alcohols leads to thecorresponding aldehydes of the formula R--A¹ --CHO, which can beconverted, using hydroxylamine, into the corresponding oximes of theformula R--A¹ --CH═NOH and, using compounds of the formula HNR¹ R², intothe corresponding aldehyde-ammonias of the formula R--A¹ --CHOH--NR¹--R² or imines of the formula R--A¹ --CH═NR¹. Unsaturated nitriles ofthe formula R--C(CH₃)═CH--CN can be prepared, for example, from theketones mentioned, of the formula R--COCH₃, and cyanoacetic acid.

Among the starting compounds of Formula II, amides of the formula R--A¹--CONR¹ R² and nitriles of the formula R--A¹ --CN are preferred.

The starting compounds of Formula II can be converted into compounds ofFormula I, for example, by catalytic hydrogenation or with nascenthydrogen, with complex metal hydrides or with other chemical reducingagents. The methods of reduction which are the most suitable for theindivdual starting materials generally depend on the nature of thefunctional group Y and are familiar to the expert from the data of theliterature. Thus, nitriles, amines of the formulae R--A--NH--W orR--A--N(W)₂, oximes and aldehyde-ammonias, for example can behydrogenated catalytically with particular advantage. On the other hand,the acid amides are reduced particularly advantageously with complexmetal hydrides or with diborane.

Noble metal catalysts, nickel catalysts or cobalt catalysts, forexample, and also mixed catalysts, such as copperchromium oxide, aresuitable for catalytic hydrogenations. Noble metals which can be usedare primarily platinum and palladium, which can be present on supports(for example, on charcoal, calcium carbonate or strontium carbonate), inthe form of oxides (for example, platinum oxide) or in a finely dividedform. Nickel catalysts and cobalt catalysts are preferable employed asRaney metals. Hydrogenation can be carried out preferably at pressuresof about 1 to 200 atms. and at temperatures of about -80° to +150°,preferably 20° to 100°. The hydrogenation is carried out in the presenceof an inert solvent, for example, an alcohol, such as methanol, ethanolor isopropanol, or carboxylic acid, such as acetic acid, an ester, suchas ethyl acetate, or an ether, such as tetrahydroguran (THF) or dioxane.It is also possible to use solvent mixtures, including mixturescontaining water. In addition, it can be advantageous to add a base,such as sodium hydroxide or potassium hydroxide or ammonia, whenhydrogenating, for example, when hydrogenating nitriles.

Complex metal hydrides, such as LiAlH₄, NaBH₄ or NaAl--(OCH₂ CH₂ OCH₃)₂H₂, and diborane can be employed as reducing agents, if desired with theaddition of a catalyst such as BF₃, AlCl₃ or LiBr. Suitable solvents forthis purpose are, in particular, ethers, such as diethyl ether, THF,dioxane, 1,2-dimethoxyethane or diglyme, and hydrocarbons, such asbenzene. Solvents suitable for reductions with NaBH₄ are, above all,alcohols, such as methanol or ethanol. In this method it is preferableto reduce at temperatures of about -80° to +150°, particularly about 20°to 120°.

A further suitable method of reduction is with nascent hydrogen. Thiscan be produced, for example, by treating metals with acids or bases.For example, the systems zinc/acid, zinc/alkali metal hydroxidesolution, iron/acid and tin/acid can be used. Examples of suitable acidsare hydrochloric acid and/or acetic acid. An alkali metal such assodium, in an alcohol, such as ethanol, isopropanol, n-butanol, amylalcohol or isoamyl alcohol, or in phenol can also be used as thereducing agent, and also, for example, an aluminum-nickel alloy in analkaline aqueous solution or alkaline aqueous-alcoholic solution, aswell as sodium amalgam or aluminium amalgam in an aqueous-alcoholicsolution or aqueous solution. The reaction temperatures in these methodsare about 0° to about 150°, preferably about 20° to 120°.

The starting compounds of Formula II can also be converted intocompounds of Formula I by cathodic reduction, preferably in anaqueous-alcoholic or aqueous acetic acid medium. Examples of othersuitable reducing agents are sodium dithionite in an aqueous-alcoholicor alkaline solution, and also iron-II hydroxide, tin-II chloride,hydrogen sulfide, hydrogen sulfides, sulfides, polysulfides andhydrazine, all of which can be used in accordance with conditionsindicated in the literature for reductions of this kind.

Selective reductions are also possible by selection of reagents andreaction conditions. Thus, Schiff's bases which contain a C--C doublebond in the radical A¹, can be reduced, using LiAlH₄, to give thecorresponding unsaturated amines.

The compounds of Formula I can also be obtained by solvolysis,preferably hydrolysis, from starting materials which otherwise,correspond to Formula I but wherein the amino group and/or the hydroxylgroup is present in a functionally modified form.

The starting compounds of the solvolysis are, in general, new, but theycan be prepared analogously to methods which are in themselves known.Examples of these starting materials are acyl derivatives of the aminesof Formula I, particularly the amides of the formula R--A--NR¹ --Ac(wherein Ac is any desired acyl radical, other than R², the nature ofwhich is not critical, since it is split off in the solvolysis, butwhich preferably is of 7 - 10 carbon atoms, for example, aroyl of up to10 carbon atoms, such as benzoyl). The amides mentioned can also beobtained, for example, by Friedel-Crafts alkylation of the biphenyls ofthe formula R--H, using halogeno-amides of the formula Cl--A--NR¹ --Acor Br--A--NR¹ --Ac. Other starting compounds are isocyanates of theformula R--A--NCO, which are formed as non-isolated intermediateproducts in the Hofmann degradation of corresponding acid amides of theformula R--A--CONH₂, in the Curtius degradation of corresponding azidesof the formula R--A--CON₃, in the Lossen degradation of correspondinghydroxamic acids of the formula R--A--CO--NHOH or in the Schmidtdegradation of corresponding carboxylic acids of the formula R--A--COOH.The carboxylic acids of the formula R--A--COOH on which the startingmaterials for these degradation reactions are based, can be obtained,for example, by Friedel-Crafts acylation of the biphenyls or diphenylethers of the formula R--H, using succinic anhydride, to give theketo-acids of the formula R--COCH₂ CH₂ COOH, and subsequent reactionwith methylmagnesium iodide to give hydroxy acids of the formulaR--C(OH)(CH.sub. 3)--CH₂ CH₂ COOH and, if desired, subsequentdehydration and/or reduction.

Examples of starting compounds for the solvolysis in which the OH groupis functionally modified, are the corresponding alcoholates,particularly the magnesium alcoholates or lithium alcoholates, such asare formed as reaction products in Grignard reactions or in reactionswith organolithium compounds, the esters (for example, the carboxylicacid esters wherein the carboxylic acid radical preferably is of up to 7carbon atoms, for example, acetyl or benzoyl, the alkylsulphonic orarylsulphonic acid esters wherein the alkyl radical preferably is of 1 -6 carbon atoms and the aryl radical preferably is of 6 - 10 carbonatoms) and the ethers (for example, the alkyl ethers wherein alkylpreferably is of up to 6 carbon atoms, the aryl ethers wherein arylpreferably is of 6 - 10 carbon atoms, and the aralkyl ethers whereinaralkyl preferably is of 7 - 11 carbon atoms). The boric acid esterswhich are intermediately formed in the oxidative hydroboronation, can,for example, also be used. In addition, a chlorine atom or iodine atomcan be used instead of the hydroxyl group, the corresponding hydrogenhalide acid esters then being present.

The magnesium alcoholates mentioned can be obtained, for example, byreacting ketones of the formula R--CO--(CH₂)_(n+1) --Z with methylmagnesium iodide or by reacting arylmagnesium halides of the formulaR-MgCl or R-MgBr with ketones of the formula CH₃ CO--(CH₂)_(n+1) --Z.Halides of the formula R--CBr(CH₃)--(CH₂)_(n+1) --Z orR--CCl(CH₃)--(CH₂)_(n+1) --Z can be prepared, for example, byhalogenation of acid amides of the formula R--A--COZ and subseqeuntreduction with LiAlH₄. The corresponding esters of the formula R--C(OAc)(CH₃)'(CH₂)_(n+1) --Z can be prepared from the halides by reaction withpotassium acylates, for example, potassium acetate.

The solvolysis of these compounds is preferably carried out by theaction of a solvent such as water (hydrolysis) or an alcohol preferablyof 1 - 4 carbon atoms (alcoholysis) in the presence of an acid or basiccatalyst, for example, a mineral acid, such as sulfuric acid orhydrochloric acid, a metal hydroxide, such as sodium hydroxide,potassium hydroxide, calcium hydroxide, barium hydroxide, lead hydroxideor silver hydroxide, or a metal salt or ammonium salt, such as sodiumcarbonate or potassium carbonate or ammonium chloride. Methanol, ethanolor isopropanol are preferably used as the alcohol, alone or as a mixturewith water. The solvolysis is preferably carried out at temperatures ofabout 0° to about 120°.

The amides mentioned above are preferably hydrolyzed by boiling forseveral hours with aqueous, aqueous-alcoholic or alcoholic hydrochloricacid, sulfuric acid, sodium hydroxide solution or potassium hydroxidesolution. The magnesium alcoholates mentioned are preferably notisolated but, instead, after being formed in the Grignard reaction, arehydrolyzed in situ using a dilute acid, for example, suluric acid orhydrochloric acid, or using aqueous ammonium chloride solution. Thehalides and esters mentioned are preferably saponified in an aqueous oraqueous-alcoholic solution or suspension, and, if desired, a solubilizercan be present, for example, an alcohol, glycol or gylcol ether.Alkalies such as NaOH or KOH are preferably used as the saponifyingagent.

The compounds of Formula I can also be obtained by reacting a compoundof the formula R-E(III) with a compound of the formula H-Z or with areactive derivative of such a compound, for example, a metal derivative(such as potassium phthalimide). The starting compounds of formula IIIare new. They can be prepared, for example, by a Grignard reaction ofketones of the formula R--CO--(CH₂ )_(n+1) --X with CH₃ MgI, to givecarbinols of the formula R--C(OH) (CH₃)--(CH₂)_(n+1) --X and, if desiredsubsequent dehydration and/or elimination of HX and/or reduction. Thestarting compounds of the formula H-Z are, in general, known.

The reaction of compounds of Formula III with compounds of the formulaH-Z is preferably carried out at temperatures of about 0° to about 250°,preferably about 50° to 120°, and at pressures of about 1 to about 50atms. The reaction can be carried out in the presence of an inertsolvent, for example, an alcohol, such as methanol, ethanol, isopropanolor n-butanol, an ether, such as diethyl ether, diisopropyl ether, THF ordioxane, a hydrocarbon, such as benzene, toluene or xylene, an amide,such as dimethylformamide (DMF), or a sulfoxide, such asdimethylsulfoxide. If desired, a catalyst can be present, for example,sodium amide, which can also be produced in situ from sodium and liquidammonia, and also bases, such as sodium carbonate, potassium carbonate,sodium bicarbonate or potassium bicarbonate. It is also possible to usean excess of the compound of the formula H--Z as the solvent, preferablyat the boiling point. If the radical E in Formula III is the group--A--X, X is preferably Cl, Br or I. If X is an OH group which isfunctionally modified in a reactive manner, it preferably isalkylsulfonyloxy or arylsulfonyloxy preferably of up to 10 carbon atoms.Secondary amines of the formula R--A--NHalkyl can also be prepared byheating alcohols of the formula R--A--OH with alkylamines in thepresence of Raney nickel.

Morpholine derivatives of Formula I (Z═morpholino) can also be obtainedby elimination of HX from amines of Formula IV. The amines of Formula IVare new. They can be obtained, for example, by reacting halogencompounds of the formula R-A-Cl or R--A--Br with amines of the formulaHN(CH₂ CH₂ OH)--CH₂ CH₂ X, for example diethanolamine. In the compoundsof Formula IV, X is preferably OH. Dehydration of diols of this kind canbe carried out, for example, by the action of an acid catalyst, such assulfuric acid or a sulfonic acid, such as p-toluenesulfonic acid, in aninert solvent, for example a hydrocarbon, such as benzene, toluene orxylene, at temperatures of about 0 to about 150°. If the radical X inthe compounds of Formula IV is a halogen atom or an OH group which isfunctionally modified in a reactive manner, the elimination of HX ispreferably carried out, however, by the action of a base, such as NaOH,or KOH, preferably in an alcoholic or aqueous-alcoholic medium attemperatures of about 0° to about 100°.

Piperazine derivatives of Formula I (Z = a piperazino group which isunsubstituted in the 4-position or which is substituted by alkyl orhydroxyalkyl in each case of up to 6 carbon atoms) can also be obtainedby reacting an amine of Formula V with a compound of the formula H₂ NR³(for example, ammonia, methylamine or 2-hydroxyethylamine). Thecompounds of Formula V (which include the compounds of Formula IV) arenew. They can be prepared from halogen compounds of the formula R--A--Clor R--A--Br by reaction with amines of the formula HN(CH₂ CH₂ X)₂ (forexample, diethanolamine), and, if desire, OH groups which may be presentcan subsequently be converted into other X groups by reaction with, forexample, SOCl₂ or PBr₃. The reaction of amines of Formula V with thecompounds of the formula H₂ NR³ is as a rule carried out in the presenceof an inert solvent, such as benzene, toluene or xylene, at temperaturesof about 0° to about 150°, and a catalyst, for example, a strong acid,such as sulfuric acid or an organic sulfonic acid, can be added.

Halogen-containing compounds of Formula I can be obtained from thecorresponding amino compunds of Formula VI by first diazotizing thelatter, for example, by reacting with a salt or an ester of nitrous acid(such as NaNO₂ or n-butyl nitrite) in aqueous hydrochloric acid attemperatures of about -20° to +10°, and subsequently converting theresulting diazonium salt into the desired halogen compound of Formula I.Thus, the corresponding fluorine compounds are preferably obtained byreacting the diazonium salt with HBF₄ to give the diazoniumtetrafluoborate and subsequent thermal decomposition at about 100° to200° in the absence or presence of an inert solvent, such as toluene,xylene or dioxane. Decomposition at room temperature in an aqueousmedium in the presence of copper powder is also possible. If thediazotization is carried out using NaNO₂ in anhydrous hydrofluoric acid,the desired fluorine compound is obtained directly by subsequentwarming. Replacement of the diazonium group by chlorine or bromine ispreferably carried out in a hot aqueous solution in the presence of Cu₂Cl₂ or Cu₂ Br₂. The starting compounds of Formula VI can be obtained,for example, by reducing the corresponding nitro compounds and these inturn can be obtained by nitrating the corresponding unsubstitutedcompounds of Formula I.

Diphenyl ether derivatives of Formula I (R= unsubstituted or substituted4-phenoxyphenyl) can also be prepared by reacting a compound of FormulaVII or a salt of such a compound, with a compound of Formula VIII or asalt of suc a compound. The starting compounds of Formula VII can beprepared, for example, by reacting halogen compounds of the formula Q¹--R⁵ --A--Cl or Q¹ --R⁵ --A--Br with compounds of the formula HZ. Thestarting compounds of Formula VII are, in general, known. It is possibleeither to react a phenol of Formula VII (Q¹ = OH) with a compound ofFormula VIII (Q² = X) or to react a compound of Formula VII (Q¹ =X) witha phenol of Formula VIII (Q² = OH).

In this reaction, the phenols are preferably in the form of thecorresponding phenolates, particularly the corresponding sodiumphenolates or potassium phenolates. The reaction is preferably carriedout in the presence of an inert solvent, such as DMF or phosphoric acidhexamethyltriamide (HMPT), in the presence of a catalyst, such as copperpowder, at a temperature of about 50 to about 200, preferably 80° to130°.

If desired, a resulting hydroxy compound of the formula R--C(OH)(CH₃)--CH₂ --(CH₂)_(n) --Z can be dehydrated to give the correspondingunsaturated compound of the formula R--C(CH₃)═CH--(CH₂)_(n) --Z,preferably by the action of an acid catalyst, such as sulfuric acid or asulfonic acid, such as p-toluenesulfonic acid, in an inert solvent, forexample, a hydrocarbon, such as benzene or toluene, at temperatures ofabout 0° to about 150°, preferably 80° to 110°.

In addition, it is possible, if desired, to reduce the hydroxy compoundsmentioned above, of the formula R--C(OH) (CH₃)--CH₂ --(CH₂)_(n) --Z, andunsaturated compounds of the formula R--C(CH₃ ═CH--(CH₂)_(n) --Z to thesaturated compounds of the formula R--CH(CH₃)--CH₂ --(CH₂)_(n) --Z. Thereduction of the hydroxy compounds is carried out, for example, withhydriodic acid, preferably in acetic acid at temperature of 20° to(preferably) the boiling point. The unsaturated compounds can behydrogenated, preferably catalytically under the condtions indicatedabove, for example, over a noble metal catalyst, such aspalladium-on-charcoal, at room temperature and ambient pressure.

In addition, one or more chlorine atoms or bormine atoms can beintroduced into a thus-produced compound of Formula I by halogenation inaccordance with methods described in the literature. This is possible,for example, by direct reaction with elementary chlorine or bromine inan inert solvent, such as ether, tetrachloromethane or acetic acid,optionally in the presence of a catalyst such as iron filings, iodine orAlCl₃, preferably at temperatures of about -30° to 100°.

In addition, the radical Z in a resulting compound of Formula I can beconverted into another Z radical by alkylation, acylation, solvolysisand/or reduction.

For example, a resulting primary amine (I, Z = NH₂) or secondary amine(I, Z = NHalkyl) can be converted into a secondary or tertiary amine ofFormula I by treatment with an alkylating agent. Examples of suitablealkylating agents are compounds of the formulae R¹ --X, R² --X or,optionally, X--R¹ R² --X, for example, methyl chloride, methyl bromide,methyl iodide, diemthyl sulfate, p-toluenesulfonic acid methyl ester,ethyl chloride, ethyl bromide, ethyl iodide, diethyl sulfate, n-propylchloride, bromide or iodide and the like, as well as 1,4-dichlorobutane,1,4-dibromobutane, 1,4-diiodobutane, 1,5-dichloropentane,1,5-dibromopentane or 1,5-diiodopentane, or 2,2'-dichloro-, 2,2'-dibromoand 2,2'-diiodo-diethyl ether. It is also possible to condense withaldehydes or ketones with the formation of aldehyde-ammonia compounds orSchiff's bases and subsequently either to hydrogenate these areindicated above or to treat them with an alkylating agent andsubsequently hydrolyze the resulting quaternary salt. For example, aprimary amine can be converted, by condensation with benzaldehyde, intothe N-benzylidene compound and the latter can be converted, with analkyl halide, into one of its quaternary salts, which can subsequentlybe converted into the secondary amine, for example, by treatment withaqueous alcohol, with the elimination of benzaldehyde. It is alsopossible to alkylate, using aldehydes or ketones under reducingconditions, the corresponding aldehydeammonias formed as intermediateproducts. For example, one or two methyl group can be introduced bymeans of formaldehyde in the presence of formic acid. In addition, it ispossible to alkylate in the presence of Raney nickel, using an alcoholof 1 - 6 carbon atoms. The alkylation is preferably carried out in thepresence or absence of one of the inert solvents mentioned, attemperatures of about 0° to about 120° , preferably 40° to 100° , and acatalyst, preferably a base, such as potassium tert.-butylate, can alsobe present.

Suitable acylating agents for acylating resulting primary or secondaryamines of Formula I are preferably the halides (for example, chloridesor bromides) or anhydrides of carboxylic acids of 1 - 6 carbon atoms,for example, acetic anhydride, propionyl chloride, isobutyryl bromide,formic acid-acetic acid anhydride or phthalic anhydride. The addition ofa base, such as pyridine or triethylamine, in the acylation is possible,but not necessary. The acylation is preferably carried out in thepresence or absence of one of the invert solvents mentioned, forexample, benzene, at temperatures of about 0° to about 160°, preferablyabout 20° to 120°.

The radical Z in a resulting compound of Formula I (Z = phthalimido orNR¹ -acyl) can be converted into another Z radical (particularly Z =NHR¹ or 3,4-dihydro-4-oxo-phthalazin-1-yl-amino), by solvolysis. Thus,the imides and amides of Formula I mentioned above can be hydrolyzedunder the conditions indicated above, preferably using aqueous,aqueous-alcoholic or alcoholic hydrochloric acid, sulfuric acid, sodiumhydroxide solution or potassium hydroxide solution, at temperatures ofabout 0° to about 120°, preferably at the boiling point.

A special embodiment of the solvolysis is the hydrazinoysis of thephthalimido compounds of Formula I, which can be converted into thedihydrophthalazin-4-ones mentioned above with hydrazine, preferably inthe form of hydrazine hydrate in alcoholic or aqueous-alcoholic solutionat temperatures of about 20° to 80°. These dihydrophthalazin-4-ones canbe hydrolyzed to give amines of Formula I (Z -- NH₂) under milderconditions than the corresponding phthalimides, for example, bytreatment of a short time with aqueous-alcoholic mineral acid,preferably aqueous-ethanolic hydrochloric acid, at temperatures of 50°0to 80°.

In addition, it is possible to reduce an acyl group in the Z radical togive the corresponding alkyl group, by one of the methods indicatedabove, preferably using a complex metal hydride, such as LiAlH₄.

A resulting base of Formula I can be converted in the customary manner,using an acid, into the appropriate acid addition salt. Acids which canbe used for this reaction are those which give physiologicallyacceptable salts. Thus, inorganic acids can be used, for example,sulfuric acid, hydrogen halide acids, such as hydrochloric acid orhydrobromic acid, phosphoric acids, such as orthophosphoric acid, nitricacid and sulphamic acid and also organic acids, in detail, aliphatic,alicyclic, araliphatic, aromatic or heterocyclic, monobasic or polybasiccarboxylic or sulfonic acids, such as formic acid, acetic acid,propionic acid, pivalic acid, diethylacetic acid, malonic acid, succinicacid, pimelic acid, fumaric acid, maleic acid, lactic acid, tartaricacid, malic acid, benzoic acid, salicyclic acid, 3-phenylpropionic acid,citric acid, gluconic acid, ascorbic acid, nicotinic acid, isonicotinicacid, methanesulfonic acid ethanesulfonic acids, ethanedisulfonic acid,2-hydroxyethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonicacid and naphthalene-monosulfonic and -disulfonic acids.

If desired, the free bases of Formula I can be liberated from theirsalts by treatment with a strong base, such as sodium hydroxide orpotassium hydroxide or sodium carbonate or potassium carbonate.

The compounds of Formula I can contain one or more centers of asymmetry.In this case, they are usually obtained in the racemic form. Theseracemates can be resolved into their optical antipodes, mechanically orchemically, in accordance with methods which are in themselves known.Preferably, diastereomers are formed from the racemic mixture byreaction with an optically active resolving agent. Examples of suitableresolving agents are optically active acids, such as the D- and L-formsof tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid,mandelic acid, malic acid, lactic acid or the various optically activecamphorsulfonic acids, such as β-camphorsulfonic acid.

It is, of course, also possible to obtain optically active compounds ofFormula I by the methods described above, by using optically activestarting compounds.

The compounds of Formula I and their physiologically acceptable acidaddition salts are well tolerated and possess valuable pharmacologicalproperties. In particular, they possess antiphlogistic activity whichcan be demonostrated in rats, for example, in the Adjuvantarthritis testby the method of Newbould (Brit. J. Pharmacol. 21. (1963) pages 127 -136). They also possess anti-arteriosclerotic activity, cholesterolserum-level lowering activity (demonstrable in the serum of rats by themethod of Levine et al., Automation in Analytical Chemistry, TechniconSymposium 1967, Mediad, New York, pages 25 - 28), triglyceride serumlevel lowering activity (demonstrable by the method of Noble andCampbell, Clin. Chem. 16 (1970), pages 166 - 170 ), as well as,analgesic, antipyretic, enzyme-inducing and fibrinolytic activity andactivity which inhibit the aggregation of thrombocytes can be observedby methods which are currently employed for these purposes.

The compounds of Formula I and their physiologically acceptble acidaddition salts can be used as medicaments and also as intermediateproducts for the preparation of other medicaments. For example, theprimary amines of the formula I (Z = NH₂) can be converted, by reactionwith nitrous acid, into the corresponding alcohols and, by the oxidationof the latter, into the corresponding carboxylic acids, which possessanti-phlogistic activity.

The compounds of Formula I and their physiologically acceptable acidaddition salts can be used, mixed with solid, liquid and/or semi-liquidmedicinal excipients, as medicaments in human and veterinary medicine.Excipients which can be used are organic or inorganic substances whichare suitable for enteral or parenteral administration or topicalapplication and which do not react with the active compounds, forexample, water, vegetable oils, benzyl alcohols, polyethylene glycols,gelatine, lactose, starch, magnesium stearate, talc, petroleum jelly orcholesterol. Tablets, dragees, capsules, syrups, elixirs, drops orsuppositories are used in particular, for enteral administration,solutions, preferably oily or aqueous solutions, and suspensions,emulsions or implants are used for parenteral administration, andointments, creams or powders are used for topical application. The newcompounds can also be lyophilized and the resulting lyophilizates can beused, for example, for the production of injection preparations. Thesepreparations can be sterilized and/or can contain auxiliary substancessuch as lubricants, preservatives, stabilizers and/or wetting agents,emulsifiers, salts for controlling the osmotic pressure, buffersubstances, colorants, flavorings and/or aroma substances. if desired,they can also contain one or more other active compounds, for example,one or more vitamins.

The novel compounds can be administered analogously to known,commercially available antiphlogistics, preferably in dosages of about10 to 1,000 mg. particularly 30 to 300 mg, per dosage unit. The dailydosage is preferably about 0.2 to 20 mg/kg of body weight. Theparticular dose for each patient depends on diverse factors, forexample, on the activity of the particular compound employed, on age,body weight, the general condition of health, sex, the diet, the pointin time, and means, of administration, the rate of elimination, thecombination of medicaments and the severity of the particular illness,and can be determined by conventional medical techniques. Oraladministration is preferred.

Without further elaboration, it is believed that one skilled in the artcan, using the preceding description, utilize the present invention toits fullest extent. The following preferred specific embodiments are,therefore, to be construed as merely illustrative, and not limitative ofthe remainder of the disclosure in any way whatsoever.

The compounds of Formula I of the following examples are particularlysuitable for the production of pharmaceutical preparations.

In the following examples, "customary working up" denotes the following:if necessary, water is added, or dilute sodium hydroxide solution isadded, if the product is a base, the mixture is extracted with anorganic solvent which is immiscible with water (for example, benzene,choroform or dichloromethane), the phases are separated and the organicphase is dried over sodium sulfate, filtered, evaporated and purified bychromatography and/or crystallization. If the product is basic, it canalso be purified by crystallizing one of its acid addition salts.Temperatures are degrees Celsius.

EXAMPLE 1

A solution of 23.9 g of 3-p-biphenylyl-butyramide [m.p. 156°- 158°'obtainable by Friedel-Crafts acetylation of biphenyl to give4-acetylbiphenyl (m.p. 118°- 120°), reaction with bromoacetic acid ethylester/zinc to give 3-p-biphenylyl-3-hydroxy-butyric acid ethyl ester(m.p. 55°- 56°), treatment with HI/acetic acid, reaction of theresulting 3-p-biphenylyl-butyric acid (m.p. 118°- 12-°) with SOCl₂ togive the chloride, and reaction with ammonia] in 500 ml of THF is addeddropwise, while stirring, to a suspension of 7.6 g of LiAlH₄ in 250 mlof absolute THF, the mixture is boiled for 16 hours, ethyl acetate isadded, with cooling, followed by 32% sodium hydroxide solution and themixture is worked up in the customary manner to give3-p-biphenylyl-butylamine. Hydrochloride, m.p. 226°-228°.

The following can be obtained analogously from the corresponding amides:

2-p-Biphenylyl-propylamine,

2-(4'-fluoro-4-biphenylyl)-propylamine, dl-malate,

m.p. 157°-159°,

2-(4'-chloro-4-biphenylyl)-propylamine,

2-(4'-p-chlorophenoxy-phenyl)-propylamine,

3-(2-fluoro-4-biphenylyl)-butylamine,

3-(3-fluoro-4-biphenylyl)-butylamine,

3-(2'-fluoro-4-biphenylyl)-butylamine, dl-malate,

m.p. 156°-158°,

3-(3'-fluoro-4-biphenylyl)-butylamine,

3-(4'-fluoro-4-biphenylyl)-butylamine, hydrochloride, m.p. 222°-224°,

3-(2-chloro-4-biphenylyl)-butylamine,

3-(3-chloro-4-biphenylyl)-butylamine,

3-(2'-chloro-4-biphenylyl)-butylamine,

3-(3'-chloro-4-biphenylyl)-butylamine,

3-(4'-chloro-4-biphenylyl)-butylamine, tartrate, m.p. 200°-202°,hydrochloride, m.p. 256 - 259°.

3-(2-bromo-4-biphenylyl)-butylamine,

3-(3-bromo-4-biphenylyl)-butylamine,

3-(3-bromo-4-biphenylyl)-butylamine,

3-(2'-bromo-4-biphenylyl)-butylamine,

3-(3'-bromo-4-biphenylyl)-butylamine,

3-(4'-bromo-4-biphenylyl)-butylamine,

3-(2',4-difluoro-4-biphenylyl)-butylamine, dl-malate, m.p. 152-154°,

3-(2',4'-dichloro-4-biphenylyl)-butylamine,

3-(2',4'-dibromo-4-biphenylyl)-butylamine,

3-(2+,4'-dibromo-4-biphenylyl)-butylamine,

3-(2'-fluoro-4'-chloro-4-biphenylyl)-butylamine,

3-(2'-fluoro-4'-bromo-4-biphenylyl)-butylamine,

3-(2'-chloro-4'-fluoro-4-biphenylyl)-butylamine,

3-(2'-bromo-4' -fluoro-4-biphenylyl)-butylamine,

3-p-phenoxyphenyl-butylamine,

3-(4-o-fluorophenoxy-phenyl)-butylamine,

3-(4-p-fluorophenoxy-phenyl)-butylamine,

3-(4-o-chlorophenoxy-phenyl)-butylamine,

3-(4-p-chlorophenoxy-phenyl)-butylamine, hydrochloride, m.p. 125°-127° ,

3-(4-o-bromophenoxy-phenyl)-butylamine,

3-(4-p-bromophenoxy-phenyl)-butylamine,

3-[4-(2,4-difluorophenoxy)-phenyl]-butylamine,

3-[4-(2,4-dichlorophenoxy)-phenyl]-butylamine,

3-[4-(2,4-dibromophenoxy)-phenyl]-butylamine,

4-p-biphenylyl-pentylamine,

4-(4'-fluoro-4-biphenylyl)-pentylamine, dl-malate,

m.p. 159°-161°,

4-(4'-chloro-4-biphenylyl)-pentylamine and

4-(4-p-chlorophenoxy-phenyl)-pentylamine.

EXAMPLE 2

3-p-Biphenylyl-3-hydroxy-butylamine, hydrochloride, m.p. 272°-275°, isobtained analogously to Example 1, using LiAlH₄, from3-p-biphenylyl-3-hydroxybutyramide (which can be prepared from thecorresponding ethyl ester (m.p. 55°-56°) and NH₃).

The following can be obtained from the corresponding hydroxyamides:

2-p-Biphenylyl-2-hydroxy-propylamine,

2-(4'-fluoro-4-biphenylyl)-2-hydroxy-propylamine,

2-(4'-chloro-4-biphenylyl)-2-hydroxy-propylamine,

2-(4-p-chlorophenoxy-phenyl)-2-hydroxy-propylamine,

3-(2-fluoro-4-biphenylyl)-3-hydroxy-butylamine,

3-(3-fluoro-4-biphenylyl)-3-hydroxy-butylamine,

3-(2'-fluoro-4-biphenylyl)3-hydroxy-butylamine, hydrochloride, m.p.200° - 202°,

3-(3'-fluoro-4-biphenylyl)-3-hydroxy-butylamine,

3-(4'-fluoro-4-biphenylyl)-3-hydroxy-butylamine, m.p. 144°-146°.

3-(2-chloro-4-biphenylyl)-3-hydroxy-butylamine,

3-(3-chloro-4-biphenylyl)-3-hydroxy-butylamine,

3-(2'-chloro-4-biphenylyl)-3-hydroxy-butylamine,

3-(3'-chloro-4-biphenylyl)-3-hydroxy-butylamine,

3-(4'-chloro-4-biphenylyl)-3-hydroxy-butylamine, hydrochloride, m.p.290° - 293°; tartrate, m.p. 191° - 194° (decomposition),

3-(2-bromo-4-biphenylyl)-3-hydroxy-butylamine,

3-(3-bromo-4-biphenylyl)-3-hydroxy-butylamine,

3-(2'-bromo-4-biphenylyl)-3-hydroxy-butylamine,

3-(3'-bromo-4-biphenylyl)-3-hydroxy-butylamine,

3-(4'-bromo-4-biphenylyl)-3-hydroxy-butylamine,

3-(2',4'-difluoro-4-biphenylyl)-3-hydroxy-butylamine,

3-(2',4'-dichloro-4-biphenylyl)-3-hydroxy-butylamine,

3-(2',4'-difluoro-4-biphenylyl)-3-hydroxy-butylamine,

3-(2'-fluoro-4'-chloro-4-biphenylyl)-3-hydroxy-butylamine,

3-(2'-fluoro-4'-bromo-4-biphenylyl)-3-hydroxy-butylamine,

3-(2'-chloro-4'-fluoro-4-biphenylyl)-3-hydroxy-butylamine,

3-(2'-bromo-4'-fluoro-4-biphenylyl)-3-hydroxy-butylamine,

3-p-phenoxyphenyl-3-hydroxy-butylamine,

3-(4-o-fluorophenoxy-phenyl)-3-hydroxy-butylamine,

3-(4-p-fluorophenoxy-phenyl)-3-hydroxy-butylamine,

3-(4-o-chlorophenoxy-phenyl)-3-hydroxy-butylamine,

3-(4-p-chlorophenoxy-phenyl)-3-hydroxy-butylamine, m.p. 96°-98°,

3-(4-o-bromophenoxy-phenyl)-3-hydroxy-butylamine,

3-(4-p-bromophenoxy-phenyl)-3-hydroxy-butylamine,

3-[4-(2,4-difluorophenoxy)-phenyl]-3-hydroxy-butylamine,

3-[4-(2,4-dichlorophenoxy)-phenyl]-3-hydroxy-butylamine,

3-[4-(2,4-dibromophenoxy)-phenyl]-3-hydroxy-butylamine, DL-malate, m.p.88° (with decomposition)

4-p-biphenylyl-4-hydroxy-pentylamine,

4-(4'-fluoro-4-biphenylyl)-4-hydroxy-pentylamine,

4-(4'-chloro-4-biphenylyl)-4-hydroxy-pentylamine and

4-(4-p-chlorophenoxy-phenyl)-4-hydroxy-pentylamine.

EXAMPLE 3

A solution of 2.37 g of 3-p-biphenylyl-2-butenoic acid amide (which canbe prepared from the corresponding 3-hydroxy-butyramide andp-toluenesulphonic acid in toluene) in 30 ml of benzene is addeddropwise, while stirring, to a suspension of 5 g of sodium aluminiumbis-(2-methoxyethoxy)dihydride in 30 ml of benzene. The mixture isboiled overnight, cooled and carefully decomposed by means of water, andworked up in the customary manner to give3-p-biphenylyl-2-butenyl-1-amine.

The following are obtained analogously from the corresponding butenoicacid amides:

3-(2-Fluoro-4-biphenylyl)-2-butenyl-1-amine,

3-(3-fluoro-4-biphenylyl)-2-butenyl-1-amine,

3-(2'-fluoro-4-biphenylyl)-2-butenyl-1-amine,

3-(3'-fluoro-4-biphenylyl)-2-butenyl-1-amine,

3-(4'-fluoro-4-biphenylyl)-2-butenyl-1-amine,

3-(2-chloro-4-biphenylyl)-2-butenyl-1-amine,

3-(3-chloro-4-biphenylyl)-2-butenyl-1-amine,

3-(2'-chloro-4-biphenylyl)-2-butenyl-1-amine,

3-(3'-chloro-4-biphenylyl)-2-butenyl-1-amine,

3-(4'-chloro-4-biphenylyl)-2-butenyl-1-amine,

3-(2-bromo-4-biphenylyl)-2-butenyl-1-amine,

3-(3-bromo-4-biphenylyl)-2-butenyl-1-amine,

3-(2'-bromo-4-biphenylyl)-2-butenyl-1-amine,

3-(3'-bromo-4-biphenylyl)-2-butenyl-1-amine,

3-(4'-bromo-4-biphenylyl)-2-butenyl-1-amine,

3-(2',4'-difluoro-4-biphenylyl)-2-butenyl-1-amine,

3-(2',4'-dichloro-4-biphenylyl)-2-butenyl-1-amine,

3-(2',4'-dibromo-4-biphenylyl)-2-butenyl-1-amine,

3-(2'-fluoro-4'-chloro-4-biphenylyl)-2-butenyl-1-amine,

3-(2'-fluoro-4'-bromo-4-biphenylyl)-2-butenyl-1-amine,

3-(2'-chloro-4'-fluoro-4-biphenylyl)-2-butenyl-1-amine,

3-(2'-bromo-4'-fluoro-4-biphenylyl)-2-butenyl-1-amine,

3-p-phenoxyphenyl-2-butenyl-1-amine,

3-(4-o-fluorophenoxy-phenyl)-2-butenyl-1-amine,

3-(4-p-fluorophenoxy-phenyl)-2-butenyl-1-amine,

3-(4-o-chlorophenoxy-phenyl)-2-butenyl-1-amine,

3-(4-p-chlorophenoxy-phenyl)-2-butenyl-1-amine,

3-(4-o-bromophenoxy-phenyl)-2-butenyl-1-amine,

3-(4-p-bromophenoxy-phenyl)-2-butenyl-1-amine,

3-[4-(2,4-difluorophenoxy)-phenyl]-2-butenyl-1-amine,

3-[4-(2,4-dichlorophenoxy)-phenyl]-2-butenyl-1-amine and

3-[4-(2,4-dibromophenoxy)-phenyl]-2-butenyl-1-amine.

EXAMPLE 4

A solution of 27.5 g of 3-(4'-chloro-4-biphenylyl)butyramide [m.p.185° - 187°; obtainable from p-chlorobiphenyl via4-acetyl-4'-chlorobiphenyl (m.p. 100° - 103°),3-(4'-chloro-4-biphenylyl)-3-hydroxybutyric acid ethyl ester (m.p.72°-74°) and 3-(4'-chloro-4-biphenylyl)-butyric acid (m.p. 154°-156°)]in 300 ml of THF is added dropwise, while stirring, to a solution of 4.6g of diborane in 50 ml of THF, and the mixture is boiled for two hours,cooled and treated with 25% hydrochloric acid. It is then poured intowater and worked up with sodium hydroxide solution and ethyl acetate togive 3-(4'-chloro-4-biphenylyl)-butylamine. Hydrochloride, m.p.256°-259°.

EXAMPLE 5

A solution of 23.9 g of 3-(4'-fluoro-4-biphenylyl)-butyronitrile(obtainable from the amide employing p-toluenesulphonylchloride/pyridine) in 250 ml of methanol is hydrogenated for 3 hours atabout 80 ats. and 80°, after adding 8 g of KOH and 12 g of Raney nickel,and the mixture is filtered, evaporated and worked up with water anddichloromethane. After drying and evaporating the organic phase,3-(4'-fluoro-4-biphenylyl)-butylamine, hydrochloride, m.p. 222°-224°, isobtained.

EXAMPLE 6

A solution of 80 g of Na₂ S₂ O₄ in 350 ml of water is added to asolution of 27.3 g of 1-nitro-3-(4'-fluoro-4-biphenylyl)-butane[obtainable by reduction of 3-(4'-fluoro-4-biphenylyl)-butyric acid,using LiAlH₄, to give the alcohol, reaction with PBr₃ to give1-bromo-3-(4'-fluoro-4-biphenylyl)butane and reaction with NaNO₂ ] in500 ml of hot ethanol. The mixture is boiled for an hour and filteredand the solution is concentrated and worked up with aqueous sodiumhydroxide solution and chloroform to give3-(4'-fluoro-4-biphenylyl)-butylamine. Hydrochloride, m.p. 222°-224°.

EXAMPLE 7

A mixture of 24.2 g of 3-(4'-fluoro-4-biphenylyl)butanal [obtainable byoxidation of 3-(4'-fluoro-4-biphenylyl)-butanol with CrO₃ ], 40 g ofliquid ammonia and 400 ml of methanol is heated at 100° for 12 hours. Inthe course thereof, 1-hydroxy-3-(4'-fluoro-4-biphenylyl)butylamine and3-(4'-fluoro-4-biphenylyl)-butylidene-imine, which are not isolated, areprobably formed as intermediate products. 30 g of Raney nickel are thenadded and the mixture is hydrogenated for about 20 hours at 100 m and100°, and is filtered and evaporated to give3-(4'-fluoro-4-biphenylyl)-butylamine. Hydrochloride, m.p. 222°-224°.

EXAMPLE 8

25.7 g of 3-(4'-fluoro-4-biphenylyl)-butanaldoxime (obtainable from thealdehyde and hydroxylamine) are dissolved in 500 ml of ethanol andhydrogenated over 3 g of PtO₂ at 20° and normal pressure until hydrogenabsorption ceases, and the mixture is filtered and evaporated to give3-(4'-fluoro-4-biphenylyl)-butylamine. Hydrochloride, m.p. 222°-224°.

EXAMPLE 9

23.7 g of 3-(4'-fluorobiphenylyl)-2-butenoic acid nitrile (obtainablefrom 4-acetyl-4'-fluorobiphenyl and cyanoacetic acid) are dissolved in150 ml of isopropanol, 15 g of liquid NH₃ and 3 g of Raney Ni, moistwith isopropanol, are added and the mixture is hydrogenated for 4 hoursat 80° and 80 ats. After filtration and evaporation,3-(4'-fluoro-4-biphenylyl)-butylamine is obtained. Hydrochloride, m.p.222°-224°.

EXAMPLE 10

A solution of 33.3 g of N-benzyl-3-(4'-fluoro-4-biphenylyl)-1-butylamine[obtainable by reacting 3-(4'-fluoro-4-biphenylyl)-butanol with SOCl₂ ]to give 1-chloro-3-(4'-fluoro-4-biphenylyl)-butane and reaction withbenzylamine in 500 ml of methanol is hydrogenated over 8 g of 5%Pd-on-charcoal at 20° and normal pressure. After filtration andevaporation, 3-(4'-fluoro-4-biphenylyl)-butylamine is obtained.Hydrochloride, m.p. 222°-224°.

The same product can be obtained analogously fromN-benzylidene-3-(4'-fluoro-4-biphenylyl)-1-butylamine or fromN,N-dibenzyl-3-(4'-fluoro-4-biphenylyl)-1-butylamine.

EXAMPLE 11

A solution of 2.79 g of 1-isobutylideneamino-3-p-biphenylyl-butane(obtainable by boiling 3-p-biphenylylbutylamine with isobutyraldehyde inbenzene for 5 hours) in 75 ml of methanol is hydrogenated, after adding0.3 g of PtO₂, at 20° and normal pressure until hydrogen absorptionceases. The mixture is filtered and worked up in the customary manner togive 1-isobutylamino-3-p-biphenylyl-butane.

EXAMPLE 12

A solution of 2.65 g of 1-isopropylimino-3-p-biphenylyl-butane(obtainable from 3-p-biphenylyl-butanal and isopropylamine) in 25 ml ofdioxane is hydrogenated, over 0.2 g of platinum, at 20° and normalpressure until hydrogen absorption ceases. The mixture is filtered andevaporated to give 1-isopropylamino-3-p-biphenylyl-butane.

EXAMPLE 13

A solution of 2.22 g of 3-p-biphenylyl-2-buten-1-al (obtainable byreacting 4-acetylbiphenyl with 2,2-diethoxy-ethylmagnesium bromide andsubsequent treatment with p-toluenesulfonic acid) and 0.6 g ofisopropylamine in 25 ml of methanol is heated at 200° for 5 hours in atube. After cooling, 0.5 g of Raney nickel, moist with methanol, isadded and the resulting Schiff's base is hydrogenated for one hour at100 atms. and 80°. The mixture is cooled and filtered and1-isopropylamino-3-p-biphenylyl-butane is obtained.

EXAMPLE 14

A solution of 2.63 g of 1-isopropylimino-3-p-biphenylyl-2-butene(obtainable from 3-p-biphenylyl-2-butenal and isopropylamine) in 20 mlof absolute ether is added dropwise to a solution of 0.6 g of LiAlH₄ in20 ml of absolute ether. The mixture is then boiled for 5 hours, wateris added carefully and the mixture is worked up in the customary mannerto give 1-isopropylamino-3-p-biphenylyl-2-butene.

EXAMPLE 15

A solution of 2.77 g of 1-pyrrolidino-3-p-biphenylyl-1-butene(obtainable from 3-p-biphenylyl-butanal and pyrrolidine) in 35 ml ofethanol is hydrogenated, over 0.5 g of Raney nickel, for 3 hours at 6atms and 60°. The catalyst is filtered off and the solution isevaporated to give 1-pyrrolidino-3-p-biphenylyl-butane.

EXAMPLE 16

1.5 g of zinc dust are added, while stirring, to a solution of 2.39 g of3-p-biphenylyl-butanaldoxime in 25 ml of acetic acid. The mixture isstirred for a further 4 hours, filtered, diluted with water, renderedalkaline with ammonia and extracted with chloroform. After the customaryworking up, 3-p-biphenylyl-butylamine is obtained. Hydrochloride, m.p.226°-228°.

EXAMPLE 17

The following are obtained analogously to Example 1, using LiAlH₄, fromthe corresponding diethylamides, morpholides or piperidides:

1-Diethylamino-3-(4'-chloro-4-biphenylyl)-butane, m.p. 42°-44°,

1-piperidino-3-p-biphenylyl-butan-3-ol, m.p. 102°-104°,

1-piperidino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol, m.p. 107°-109°,

1-piperidino-3-(4'-bromo-4-biphenylyl)-butan-3-ol, m.p. 89°-91°.

1-piperidino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol, m.p. 73°-74°,

1-piperidino-3-(4-p-bromophenoxy-phenyl)-butan-3-ol, m.p. 73°-75°,

1-morpholino-3-p-biphenylyl-butan-3-ol, m.p. 116°-118°,

1-morpholino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol, m.p. 152°-154°,

1-morpholino-3-(4'-chloro-4-biphenylyl)-butan-3-ol, m.p. 106°-108°,

1-morpholino-3-(4'-bromo-4-biphenylyl)-butan-3-ol, m.p. 97°-99° and

1-morpholino-3-(4-p-chlorophenoxy-phenyl)-butan-3ol, m.p. 66°-67°.

EXAMPLE 18

1-piperidino-3-p-biphenylyl-butan-3-ol, m.p. 102°-104°, is obtainedanalogously to Example 1, using LiAlH₄, from1-(2-oxo-piperidino)-3-p-biphenylyl-butan-3-ol (obtainable from3-p-biphenylyl-3-hydroxy-butylamine and 5-bromovaleryl bromide).

EXAMPLE 19

A mixture of 3.23 g of 1-(4-oxopiperidino)-3-p-biphenylyl-butan-3-ol(obtainable from 1-chloro-3-p-biphenylyl-butan-3-ol and 4-piperidone),1.5 g of KOH, 2.5 ml of 85% hydrazine and 25 ml of diethylene glycol iswarmed at 100° for 1 hour. The temperature is raised slowly until thehydrazone is decomposed, and the mixture is boiled for a further 4hours, cooled and worked up in the customary manner to give1-piperidino-3-p-biphenylyl-butan-3-ol, m.p. 102° - 104°.

EXAMPLE 20

4.05 g of 1-dibenzylamino-3p-biphenylyl-butane (obtainable by reacting1-chloro-3-p-biphenylyl-butan-3-ol with dibenzylamine to give1-dibenzylamino-3p-biphenylyl-butan-3-ol and subsequent reduction withHI) is dissolved in 50 ml of ethyl acetate and hydrogenated, over 0.5 g.of 10% Pd-on-charcoal, at 20° and 1 at. until hydrogen absorptionceases. The mixture is filtered and evaporated to give3-p-biphenylyl-butylamine. Hydrochloride, m.p. 226° - 228°.

EXAMPLE 21

A solution of 27.1 g of 4-(4'-fluoro-4-biphenylyl)-pentanoic acid amide[obtainable by reacting 4-fluorobiphenyl with succinic anhydride/AlCl₃to give 4-(4'-fluoro-4-biphenylyl)-4-oxobutanoic acid, reaction with CH₃MgI to give 4-(4'-fluoro-4-biphenylyl)-4-hydroxy-pentanoic acid,dehydroxylation with HI/acetic acid to give4-(4'-fluoro-4-biphenylyl)-pentanoic acid, conversion into the chlorideemploying SOCl₂ and reaction with NH₃ ] in 150 ml of dioxane is addeddropwise at 0° to a solution of 24 g of bromine in 120 ml of 20%potassium hydroxide solution. The mixture is stirred for a further 1hour, taken up in ether, the phases are separated and the organic phaseis dried over sodium sulfate and evaporated. The crude product obtainedis boiled for 20 hours with 60 g of KOH, 250 ml of methanol and 65 ml ofwater, in the course of which 3-(4'-fluoro-4-biphenylyl)-butyl-isocyanate, which is not isolated, isformed. After cooling, the mixture is worked up using water and ether togive 3-(4'-fluoro-4-biphenylyl)-butylamine, hydrochloride; m.p.222°-224°.

EXAMPLE 22

A solution of 24.4 g of 1-amino-3-(4'-fluoro-4-biphenylyl)-propan-3-one[obtainable by reacting 1-chloro-3-(4'-fluoro-4-biphenylyl)-propan-3-onewith potassium phthalimide and subsequent hydrolysis] in 200 ml of THFis added dropwise, while stirring, at 20° to a Grignard solutionprepared from 30 g of CH₃ I and 5 g of magnesium in 1000 ml of ether.The mixture is stirred for a further 4 hours, the resulting alcoholateis decomposed by means of water and dilute sulfuric acid, and themixture is worked up in the customary manner to give3-(4-fluoro-4-biphenylyl)-3-hydroxybutylamine, m.p. 144° - 146°.

1-Morpholino-3-(4'-chloro-4-biphenylyl)-butan-3-ol, m.p. 106° - 108°, isobtained analogously by hydrolysis of the alcoholate prepared from1-morpholino-3-(4'-chloro-4-biphenylyl)-propan-3-one (obtainable from4-p-chlorophenylacetophenone, morpholine and formaldehyde) and CH₃ MgI.

EXAMPLE 23

4.35 g of 1-aminobutan-3-one in 400 ml of ether are added dropwise,while stirring, at 20° to a Grignard solution formed from 25.1 g of4'-fluoro-4-bromo-biphenyl (obtainable by brominating 4-fluoro-biphenyl)and 2.43 g of magnesium in 1,000 ml of ether, the mixture is stirred fora further two hours, the resulting alcoholate is decomposed employingdilute sulfuric acid, and the mixture is worked up in the customarymanner to give 3-(4'-fluoro-4-biphenylyl)-3-hydroxybutylamine, m.p.144° - 146°.

EXAMPLE 24

3.59 g of 3-bromo-3-(4'-fluoro-4-biphenylyl)butylamine hydrochloride[obtainable by reacting 3-hydroxy-3-(4'-fluoro-4-biphenylyl)-butyramidewith PBr₃ to give 3-bromo-3-(4'-fluoro-4-biphenylyl)-butyramide andreduction with LiAlH₄ ] are dissolved in a mixture of 15 ml of acetoneand 15 ml of water, 1 drop of sulfuric acid is added, and the mixture iswarmed to 45° for 4 hours and worked up in the customary manner to give3-(4'-fluoro-4-biphenylyl)-3-hydroxybutylamine, m.p. 144° - 146°. Alittle 3-(4'-fluoro-4-biphenylyl)-2-butenylamine, which can be removedby chromatography (over SiO₂), is formed as a by-product.

EXAMPLE 25

30.1 g of 3-acetoxy-3-(4'-fluoro-4-biphenylyl)-1-butylamine [obtainablefrom 3-bromo-3-(4'-fluoro-4-biphenylyl)-1-butylamine and potassiumacetate] are boiled for 2 hours with 20 g of KOH in 500 ml of methanol,and the mixture is worked up with water and chloroform to give3-(4'-fluoro-4-biphenylyl)-3-hydroxybutylamine, m.p. 144° - 146°.

EXAMPLE 26

24.2 g of 3-(4'-fluoro-4-biphenylyl)-1-buten-3-ol (obtainable from4-acetyl-4'-fluorobiphenyl and vinylmagnesium bromide) are heated with 8g of ammonia and 0.25 g of sodium for 8 hours at 180° - 200°, and themixture is cooled and worked up with water and chloroform to give3-(4'-fluoro-4-biphenylyl)-3-hydroxybutylamine, m.p. 144° - 146°.

3-(4'-Fluoro-4-biphenylyl)-butylamine, hydrochloride, m.p. 222° - 224°,is obtained analogously from 3-(4'-fluoro-4-biphenylyl)-1-butene.

EXAMPLE 27

A solution of 26.25 g of 1-chloro-3-(4'-fluoro-4-biphenylyl)-butane[obtainable by a Friedel-Crafts reaction of 4-fluoro-biphenyl with3-chloropropionyl chloride to give4'-fluoro-4-(3-chloropropionyl)-biphenyl (m.p. 96° - 97° ), reactionwith CH₃ MgI to give 1-chloro-3-(4'-fluoro-4-biphenylyl)-butan-3-ol(m.p. 78° - 79° ) and reduction using HI] in 150 ml of absolute ethanolis added dropwise at 0° to a solution of 10 g of NH₃ in 150 ml ofabsolute ethanol. The solution is stirred for a further 2 hours at 20°,concentrated and worked up with aqueous sodium hydroxide solution andether to give 3-(4'-fluoro-4-biphenylyl)-butylamine; hydrochloride, m.p.222° - 224°.

EXAMPLE 28

A solution of 2.6 g of 1-chloro-3-p-biphenylylbutan-3-ol [m.p. 68° -70°; obtainable by a Friedel-Crafts reaction of biphenyl with3-chloropropionyl chloride to give 4-(3-chloropropionyl)-biphenyl andreaction with CH₃ MgI; or 3.05 g of 1-bromo-3-p-biphenylyl-butan-3-ol or3.96 g of 1-p-toluenesulfonyloxy-3-p-biphenylyl-butan-3-ol] and 30g ofmethylamine in 100 ml of methanol is heated at 120° for 2 hours in anautoclave. After cooling and working up in the customary manner,1-methylamino-3-p-biphenylyl-butan-3-ol is obtained.

The following are obtained analogously from the corresponding chlorineor bromine compounds:

1-Methylamino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-methylamino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-methylamino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-ethylamino-3-p-biphenylyl-butan-3-ol,

1-ethylamino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-ethylamino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-ethylamino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-n-propylamino-3-p-biphenylyl-butan-3-ol,

1-n-propylamino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-n-propylamino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-n-propylamino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-isopropylamino-3-p-biphenylyl-butan-3-ol,

1-isopropylamino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-isopropylamino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-isopropylamino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-n-butylamino-3-p-biphenylyl-butan-3-ol,

1-n-butylamino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-n-butylamino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-n-butylamino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-isobutylamino-3-p-biphenylyl-butan-3-ol,

1-isobutylamino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-isobutylamino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-isobutylamino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-sec.-butylamino-3-p-biphenylyl-butan-3-ol,

1-sec.-butylamino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-sec.-butylamino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-sec.-butylamino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-tert.-butylamino-3-p-biphenylyl-butan-3-ol,

1-tert.-butylamino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-tert.-butylamino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-tert.-butylamino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-n-pentylamino-3-p-biphenylyl-butan-3-ol and

1-n-hexylamino-3-p-biphenylyl-butan-3-ol.

EXAMPLE 29

2.6 g of 1-chloro-3-p-biphenylyl-butan-3-ol are boiled with 30 ml ofmorpholine for 1.5 hours and the mixture is cooled and worked up in thecustomary manner to give 1-morpholino-3-p-biphenylyl-butan-3-ol, m.p.116° -118°.

The following are obtained analogously from the corresponding chlorineor bromine compounds:

1-Morpholino-2-p-biphenylyl-propan-2-ol,

1-morpholino-2-(4'-fluoro-4-biphenylyl)-propan-2-ol,

1-morpholino-2-(4'-chloro-4-biphenylyl)-propan-2-ol,

1-morpholino-2-(4'-bromo-4-biphenylyl)-propan-2-ol,

1-morpholino-2-(4-p-chlorophenoxy-phenyl)-propan-2-ol,

1-morpholino-3-(2'-fluro-4-biphenylyl)-butan-3-ol,

1-morpholino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol, m.p. 152° - 154°,

1-morpholino-3-(2'-chloro-4-biphenylyl)-butan-3-ol,

1-morpholino-3-(4'-chloro-4-biphenylyl)-butan-3-ol, m.p. 106° -108°,

1-morpholino-3-(2'-bromo-4-biphenylyl)-butan-3-ol,

1-morpholino-3-(4'-bromo-4-biphenylyl)-butan-3-ol, m.p. 97° -99°,

1-morpholino-3-(2',4'-difluoro-4-biphenylyl)-butan-3-ol,

1-morpholino-3-(2',4'-dichloro-4-biphenylyl)-butan-3-ol,

1-morpholino-3-(2',4'-dibromo-4-biphenylyl)-butan-3-ol,

1-morpholino-3-p-phenoxy-phenyl-butan-3-ol,

1-morpholino-3-(4-o-fluorophenoxy-phenyl)-butan-3-ol,

1-morpholino-3-(4-p-fluorophenoxy-phenyl)-butan-3-ol,

1-morpholino-3-(4-o-chlorophenoxy-phenyl)-butan-3-ol,

1-morpholino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol, m.p. 66° - 67°,

1-morpholino-3-(4-o-bromophenoxy-phenyl)-butan-3-ol,

1-morpholino-3-(4-p-bromophenoxy-phenyl)-butan-3-ol,

1-morpholino-3-[4-(2,4-difluorophenoxy)-phenyl]-butan-3-ol,

1-morpholino-3-[4-(2,4-dichlorophenoxy)-phenyl]-butan-3-ol,

1-morpholino-3-[4-(2,4-dibromophenoxy)-phenyl]-butan-3-ol,

1-morpholino-4-p-biphenylyl-pentan-4-ol,

1-morpholino-4-(4'-fluoro-4-biphenylyl)-pentan-4-ol,

1-morpholino-4-(4'-chloro-4-biphenylyl)-pentan-4-ol,

1-morpholino-4-(4'-bromo-4-biphenylyl)-pentan-4-ol and

1-morpholino-4-(4-p-chlorophenoxy-phenyl)-pentan-4-ol.

EXAMPLE 30

The following are obtained, analogously to Example 29, from thecorresponding chlorine or bromine compounds, using pyrrolidine,piperidine, 4 -methylpiperidine, homopiperidine or piperazine:

1-Pyrrolidino-3-p-biphenylyl-butan-3-ol,

1-pyrrolidino-3-(2'-fluoro-4-biphenylyl)-butan-3-ol,

1-pyrrolidino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-pyrrolidino-3-(2'-chloro-4-biphenylyl)-butan-3-ol,

1-pyrrolidino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-pyrrolidino-3-(2'-bromo-4-biphenylyl)-butan-3-ol,

1-pyrrolidino-3-(4'-bromo-4-biphenylyl)-butan-3-ol,

1-pyrrolidino-3-(2',4'-difluoro-4-biphenylyl)-butan-3-ol,

1-pyrrolidino-3-(2',4'-dichloro-4-biphenylyl)-butan-3-ol,

1-pyrrolidino-3-(2',4'-dibromo-4-biphenylyl)-butan-3-ol,

1-pyrrolidino-3-p-phenoxy-phenyl-butan-3-ol,

1-pyrrolidino-3-(4-o-fluorophenoxy-phenyl)-butan-3-ol,

1-pyrrolidino-3-(4-p-fluorophenoxy-phenyl)-butan-3-ol,

1-pyrrolidino-3-(4-o-chlorophenoxy-phenyl)-butan-3-ol,

1-pyrrolidino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-pyrrolidino-3-(4-o-bromophenoxy-phenyl)-butan-3-ol,

1-pyrrolidino-3-(4-p-bromophenoxy-phenyl)-butan-3-ol,

1-pyrrolidino-3-[4-(2,4-difluorophenoxy)-phenyl]-butan-3-ol,

1-pyrrolidino-3-[4-(2,4-dichlorophenoxy)-phenyl]-butan-3-ol,

1-pyrrolidino-3-[4-(2,4-dibromophenoxy)-phenyl]-butan-3-ol,

1-piperidino-2-p-biphenylyl-propan-2-ol,

1-piperidino-2-(4'-fluoro-4-biphenylyl)-propan-2-ol,

1-piperidino-2-(4'-chloro-4-biphenylyl)-propan-2-ol,

1-piperidino-2-(4'-bromo-4-biphenylyl)-propan-2-ol, hydrochloride, m.p.245° - 247°,

1-piperidino-2-(4-p-chlorophenoxy-phenyl)-propan-2-ol,

1-piperidino-3-p-biphenylyl-butan-3-ol, m.p. 102° - 104°,

1-piperidino-3-(2'-fluoro-4-biphenylyl)-butan-3-ol,

1-piperidino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol, m.p. 107°-109°,hydrochloride, m.p. 238° - 242°,

1-piperidino-3-(2'-chloro-4-biphenylyl)-butan-3-ol,

1-piperidino-3-(4'-chloro-4-biphenylyl)-butan-3-ol, m.p. 90°-91°,

1-piperidino-3-(2'-bromo-4-biphenylyl)-butan-3-ol,

1-piperidino-3-(4'-bromo-4-biphenylyl)-butan-3-ol, m.p. 89°-91°,

1-piperidino-3-(2',4'-difluoro-4-biphenylyl)-butan-3-ol,

1-piperidino-3-(2',4'-dichloro-4-biphenylyl)-butan-3-ol,

1-piperidino-3-(2',4'-dibromo-4-biphenylyl)-butan-3-ol,

1-piperidino-3-p-phenoxy-phenyl-butan-3ol,

1-piperidino-3-(4-o-fluorophenoxy-phenyl)-butan-3-ol,

1-piperidino-3-(4-p-fluorophenoxy-phenyl)-butan-3-ol, m.p. 50°-51°,

1-piperidino-3-(4-o-chlorophenoxy-phenyl)-butan-3-ol,

1-piperidino-3-(4-o-chlorophenoxy-phenyl)-butan-3-ol, m.p. 73°-75°,

1-piperidino-3-(4-o-bromophenoxy-phenyl)-butan-3-ol,

1-piperidino-3-(4-p-bromophenoxy-phenyl)-butan-3-ol, m.p. 73°-75°,

1-piperidino-3-[4-(2,4-difluorophenoxy)-phenyl]-butan-3-ol,

1-piperidino-3-[4-(2,4-dichlorophenoxy)-phenyl]-butan-3-ol,

1-priperidino-3-[4-(2,4-dibromophenoxy)-phenyl]-butan-3-ol,

1-piperidino-4-p-biphenylyl-pentan-4-ol,

1-piperidino-4-(4'-fluoro-4-biphenylyl)-pentan-4-ol,

1-piperidino-4-(4'-chloro-4-biphenylyl)-pentan-4-ol,

1-piperidino-4-(4'-bromo-4-biphenylyl)-pentan-4-ol, hydrochloride, m.p.282° -283°,

1-piperidino-4-(4-p-chlorophenoxy-phenyl)-pentan-4-ol,

1-(4-methylpiperidino)-3-p-biphenylyl-butan-3-ol,

1-(4-methylpiperidino)-3-(2'-fluoro-4-biphenylyl)-butan-3-ol,

1-(4-methylpiperidino)-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,hydrochloride, m.p. 222°,

1-(4-methylpiperidino)-3-(2'-chloro-4-biphenylyl)-butan-3-ol,

1-(4-methylpiperidino)-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-(4-methylpiperidino)-3-(2'-bromo-4-biphenylyl)-butan-3-ol,

1-(4-methylpiperidino)-3-(4'-bromo-4-biphenylyl)-butan-3-ol,

1-(4-methylpiperidino)-3-(2',4'-difluoro-4-biphenylyl)-butan-3-ol,

1-(4-methylpiperidino)-3-(2',4'-dichloro-4-biphenylyl)-butan-3-ol,

1-(4-methylpiperidino)-3-(2',4'-dibromo-4-biphenylyl)-butan-3-ol,

1-(4-methylpiperidino)-3-p-phenoxy-phenyl-butan-3-ol,

1-(4-methylpiperidino)-3-(4-o-fluorophenoxy-phenyl)-butan-3-ol,

1-(4-methylpiperidino)-3-(4-fluorophenoxy-phenyl)-butan-3-ol,

1-(4-methylpiperidino)-3-(4-o-chlorophenoxy-phenyl)-butan-3-ol,

1-(4-methylpiperidino)-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol, m.p.81° - 82°,

1-(4-methylpiperidino)-3-(4-o-bromophenoxy-phenyl)-butan-3-ol,

1-(4-methylpiperidino)-3-(4-p-bromophenoxy-phenyl)-butan-3-ol, m.p.78° - 79.5°,

1-(4-methylpiperidino)-3-[4-(2,4-difluorophenoxy)-phenyl]-butan-3-ol,

1-(4-methylpiperidino)-3-[4-(2,4-dichlorophenoxy)-phenyl]-butan-3-ol,

1-(4-methylpiperidino)-3-[4-(2,4-dibromophenoxy)-phenyl]-butan-3-ol,

1-homopiperidino-3-p-biphenylyl-butan-3-ol, m.p. 66° - 67°,

1-homopiperidino-3-(2'-fluoro-4-biphenylyl)-butan-3-ol, hydrochloride,m.p. 160° - 161°,

1-homopiperidino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-homopiperidino-3-(2'-chloro-4-biphenylyl)-butan-3-ol,

1-homopiperidino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-homopiperidino-3-(2'-bromo-4-biphenylyl)-butan-3-ol,

1-homopiperidino-3-(4'bromo-4-piphenylyl)-butan-3-ol,

1-homopiperidino-3-(2', 4'-difluoro-4-biphenylyl)-butan-3-ol,

1-homopiperidono-4-(2',4'-dichloro-4biphenylyl)-butan-3-ol,

1-homopiperidino-3-(2', 4'-dibromo-4-biphenylyl)-butan-3-ol,

1-homopiperidino-3-p-phenoxy-phenyl-butan-3-ol,

1-homopiperidino-3-(4-o-fluorophenoxy-phenyl)-butan-3-ol,

1-homopiperidino-3-(4-p-fluorophenoxy-phenyl)-butan-3-ol,

1-homopiperidino-3-(4-o-chlorophenoxy-phenyl)-butan-3-ol,

1-homopiperidino-4-(4-p-chlorophenoxy-phenyl)-butan-3-ol, hydrochloride,m.p. 180° - 181°,

1-homopiperidino-3-(4-o-bromophenoxy-phenyl)-butan-3-ol,

1-homopiperidino-3-(4-p-bromophenoxy-phenyl)-butan-3-ol,

1-homopiperidino-4-[4-(2,4-difluorophenoxy)-phenyl]-butan-3-ol,

1-homopiperidino-3-[4-(2,4-dichlorophenoxy)-phenyl]-butan-3-ol,

1-homopiperidino-3-[4-(2,4-dibromophenoxy)-phenyl]-butan-3-ol,

1-piperazino-3-p-biphenylyl-butan-3-ol,

1-piperazino-3-(2'-fluoro-4-biphenylyl)-butan-3-ol,

1-piperazino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol, m.p. 168° - 169°,

1-piperazino-3-(2'-chloro-4-biphenylyl)-butan-3-ol,

1-piperazino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-piperazino-3-(2'-bromo-4-biphenylyl)-butan-3-ol,

1-piperazino-3-(4'-bromo-4-biphenylyl)-butan-3-ol,

1-piperazino-3-(2',4'-difluoro-4-biphenylyl)-butan-3-ol,

1-piperazino-3-(2',4'-dichloro-4-biphenylyl)-butan-3-ol,

1-piperazino-3-(2',4'-dibromo-4-biphenylyl)-butan-3-ol,

1-piperazino-3-p-phenoxy-phenyl-butan-3-ol,

1-piperazino-3-(4-o-fluorophenoxy-phenyl)-butan-3-ol,

1-piperazino-3-(4-p-fluorophenoxy-phenyl)-butan-3-ol,

1-piperazino-3-(4-o-chlorophenoxy-phenyl)-butan-3-ol,

1-piperazino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-piperazino-3-(4-o-bromophenoxy-phenyl)-butan-3-ol,

1-piperazino-3-(4-p-bromophenoxy-phenyl)-butan-3-ol,

1-piperazino-3-[4-(2,4-difluorophenoxy)-phenyl]-butan-3-ol,

1-piperazino-3-[4-(2,4-dichlorophenoxy)-phenyl]-butan-3-ol and

1-piperazino-3-[4-(2,4-dibromophenoxy)-phenyl]-butan-3-ol.

EXAMPLE 31

The following are obtained, analogously to Example 29, from thecorresponding chlorine or bromine compounds, using di-n-propylamine,diisopropylamine, di-n-butylamine, diisobutylamine, di-n-pentylamine,di-n-hexylamine, 2-dimethylamino-ethylamine, 2-diethylamino-ethylamine,3-dimethylamino-propylamine, 2-methylpiperidine, 3-methylpiperidine,2,6-dimethylpiperidine, 1-methylpiperazine, 1-ethylpiperazine,1-n-hexylpiperazine or 1-(2-hydroxyethyl)-piperazine:

1-Di-n-propylamino-3-p-biphenylyl-butan-3-ol,

1-di-n-propylamino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-di-n-propylamino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-di-n-propylamino-3-(4-p-chlorophenoxy-phenyl)-butan-3ol,

1-diisopropylamino-3-p-biphenylyl-butan-3ol,

1-diisopropylamino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-diisopropylamino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-diisopropylamino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-di-n-butylamino-3-p-biphenylyl-butan-3-ol,

1-di-n-butylamino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-di-n-butylamino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-di-n-butylamino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-diisobutylamino-3-p-biphenylyl-butan-3-ol,

1-diisobutylamino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-diisobutylamino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-diisobutylamino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-di-n-pentylamino-3-p-biphenylyl-butan-3-ol,

1-di-n-penthylamino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-di-n-pentylamino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-di-n-pentylamino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-di-n-hexylamino-3-p-biphenylyl-butan-3-ol,

1-di-n-hexylamino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-di-n-hexylamino-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-di-n-hexylamino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-(2-dimethylamino-ethylamino)-3-p-biphenylyl-butan-3-ol,

1-(2-dimethylamino-ethylamino)-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-(2-dimethylamino-ethylamino)-3-(4'-chloro-4biphenylyl)-butan-3-ol,

1-(2-dimethylamino-ethylamino)-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-(2-diethylamino-ethylamino)-3-p-biphenylyl-butan-3-ol,

1-(2-diethylamino-ethylamino)-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,m.p. 74°; dihydrochloride, m.p. 198°,

1-(2-diethylamino-ethylamino)-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-(2-diethylamino-ethylamino)-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-(3-dimethylamino-propylamino)-3-p-biphenylyl-butan-3-ol,

1-(3-dimethylamino-propylamino)-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-(3-dimethylamino-propylamino)-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-(3-dimethylamino-propylamino)-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-(2-methylpiperidino)-3-p-biphenylyl-butan-3-ol,

1-(2-methylpiperidino)-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-(2-methylpiperidino)-3-(4'-chloro-4-biphenylyl)-butan-3ol,

1-(2-methylpiperidino)-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-(3-methylpiperidino)-3-p-biphenylyl-butan-3-ol,

1-(3-methylpiperidino)-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-(3-methylpiperidino)-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-(3-methylpiperidino)-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-(2,6-dimethylpiperidino)-3-p-biphenylyl-butan-3-ol,

1-(2,6-dimethylpiperidino)-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-(2,6-dimethylpiperidino)-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-(2,6-dimethylpiperidino)-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-(4-methyl-piperazino)-3-p-biphenylyl-butan-3-ol,

1-(4-methyl-piperazino)-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-(4-methyl-piperazino)-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-(4-methyl-piperazino)-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-(4-ethyl-piperazino)-3-p-biphenylyl-butan-3-ol,

1-(4-ethyl-piperazino)-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-(4-ethyl-piperazino)-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-(4-ethyl-piperazino)-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-(4-n-hexyl-piperazino)-3-p-biphenylyl-butan-3-ol,

1-(4-n-hexylpiperazino)-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-(4-n-hexyl-piperazino)-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-(4-n-hexyl-piperazino)-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-[4-(2-hydroxyethyl)-piperazino]-3-p-biphenylyl-butan-3-ol,

1-[4-(2-hydroxyethyl)-piperazino]-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,m.p. 76° - 78°; dihydrochloride, m.p. 246° - 247°,

1-[4-(2-hydroxyethyl)-piperazino]-3-(4'-chloro-4-biphenylyl)-butan-3-oland

1-[4-(2-hydroxyethyl)-piperazino]-3-(4-p-chlorophenoxyphenyl)-butan-3-ol.

EXAMPLE 32

2.6 g of 1-chloro-3-p-biphenylyl-butan-3-ol are heated with 30 ml ofdiethylamine at 150° for 15 hours in an autoclave, and the mixture iscooled and worked up in the customary manner to give1-diethylamino-3-p-biphenylyl-butan-3-ol.

The following are obtained analogously from the corresponding chlorineor bromine compounds:

1-Diethylamino-3-(2'-fluoro-4-biphenylyl)-butan-3ol,

1-diethylamino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-diethylamino-3-(2'-chloro-4-biphenylyl)-butan-3-ol,

1-diethylamino-3-(4'-chloro-4-biphenylyl)-butan-3-ol, m.p. 61-63°,

1-diethylamino-3-(2'-bromo-4-biphenylyl)-butan-3-ol,

1-diethylamino-3-(4'-bromo-4-biphenylyl)-butan-3-ol,

1-diethylamino-3-(2',4'-difluoro-4-biphenylyl)-butan-3-ol,

1-diethylamino-3-(2',4'-dichloro-4-biphenylyl)-butan-3-ol,

1-diethylamino-3-(4',4'-dibromo-4-biphenylyl)-butan-3-ol,

1-diethylamino-3-p-phenoxy-phenyl-butan-3-ol,

1-diethylamino-3-(4-o-fluorophenoxy-phenyl)-butan-3-ol,

1-diethylamino-3-(4-p-fluorophenoxy-phenyl)-butan-3-ol,

1-diethylamino-3-(4-o-chlorophenoxy-phenyl)-butan-3-ol,

1-diethylamino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-diethylamino-3-(4-o-bromophenoxy-phenyl)-butan-3-ol,

1-diethylamino-3-(4-p-bromophenoxy-phenyl)-butan-3-ol,

1-diethylamino-3-[4-(2,4-difluorophenoxy)-phenyl]-butan-3-ol,

1-diethylamino-3-[4-(2,4-dichlorophenoxy)-phenyl]-butan-3-ol and

1-diethylamino-3-[4-(2,4-dibromophenoxy)-phenyl]-butan-3-ol.

EXAMPLE 33

A mixture of 2.6 g of 1-chloro-3-p-biphenylyl-butan-3-ol, 2.04 g ofpotassium phthalimide and 40 ml of DMF is heated at 110° for 1.5 hours.After cooling, the mixture is worked up in the customary manner to give1-phthalimido-3-p-biphenylyl-butan-3-ol, m.p. 153° - 155°.

The following are obtained analogously from the corresponding chlorineor bromine compounds:

1-Phthalimido-3-(2'-fluoro-4-biphenylyl)-butan-3-ol, m.p. 125° -127°,

1-phthalimido-3-(4'-fluoro-4-biphenylyl)-butan-3-ol, m.p. 150° -152°,

1-phthalimido-3-(2'-chloro-4-biphenylyl)-butan-3-ol.

1phthalimido-3-(4'-chloro-4-biphenylyl)-butan-3-ol, m.p. 177°- 179 ,

1-phthalimido-3-(2'-bromo-4-biphenylyl)-butan-3-ol,

1-phthalimido-3-(4'-bromo-4-biphenylyl)-butan-3-ol,

1-phthalimido-3-(2',4'-difluoro-4-biphenylyl)-butan-3-ol, m.p. 128° -130°,

1-phthalimido-3-(2',4'-dichloro-4-biphenylyl)-butan-3-ol,

1-phthalimido-3-(2',4'-dibromo-4-biphenylyl)-butan-3-ol,

1-phthalimido-3-p-phenoxy-phenyl-butan-3-ol,

1-phthalimido-3-(4-o-fluorophenoxy-phenyl)-butan-3-ol,

1-phthalimido-3-(4-p-fluorophenoxy-phenyl)-butan-3-ol,

1-phthalimido-3-(4-o-chlorophenoxy-phenyl)-butan-3-ol,

1-phthalimido-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol, m.p. 135° - 137°,

1-phthalimido-3-(4-o-bromophenoxy-phenyl)-butan-3-ol,

1-phthalimido-3-(4-p-bromophenoxy-phenyl)-butan-3-ol,

1-phthalimido-3-[4-(2,4-difluorophenoxy)-phenyl]-butan-3-ol,

1-phthalimido-3-[4-(2,4-dichlorophenoxy)-phenyl]-butan-3-ol and

1-phthalimido-3-[4-(2,4-dibromophenoxy)-phenyl]-butan-3-ol.

EXAMPLE 34

A mixture of 2.6 g of 1-chloro-3-p-biphenylyl-butan-3-ol and 1.36 g ofimidazole is heated at 140° for 3 hours. After cooling and working up inthe customary manner, 1-(1-imidazolyl)-3-p-biphenylyl-butan-3-ol isobtained.

The following are obtained analogously from the corresponding chlorineor bromine compounds:

1-(1-imidazolyl)-3-(2'-fluoro-4-biphenylyl)-butan-3-ol,

1-(1-imidazolyl)-3-(4'-fluoro-4-biphenylyl)-butan-3-ol, m.p. 205° -207°,

1-(1-imidazolyl)-3-(2'-chloro-4-biphenylyl)-butan-3-ol,

1-(1-imidazolyl)-3-(4'-chloro-4-biphenylyl)-butan-3-ol, m.p. 201° -203°,

1-(1-imidazolyl)-3-(2'-bromo-4-biphenylyl)-butan-3-ol,

1-(1-imidazolyl)-3-(4'-bromo-4-biphenylyl)-butan-3-ol,

1-(1-imidazolyl)-3-(2',4'-difluoro-4-biphenylyl)-butan-3-ol,

1-(1-imidazolyl)-3-(2',4'-dichloro-4-biphenylyl)-butan-3-ol,

1-(1-imidazolyl)-3-(2',4'-dibromo-4-biphenylyl)-butan-3-ol,

1-(1-imidazolyl)-3-p-phenoxy-phenoxy-phenyl-butan-3-ol,

1-(1-imidazolyl)-3-(4-o-fluorophenoxy-phenyl)-butan-3-ol,

1-(1-imidazolyl)-3-(4-p-fluorophenoxy-phenyl)-butan-3-ol,

1-(1-imidazolyl)-3-(4-o-chlorophenoxy-phenyl)-butan-3-ol,

1-(1-imidazolyl)-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol, m.p. 125° -125°,

1-(1-imidazolyl)-3-(4-o-bromophenoxy-phenyl)-butan-3-ol,

1-(1-imidazolyl)-3-(4-p-bromophenoxy-phenyl)-butan-3-ol,

1-(1-imidazolyl)-3-[4-(2,4-difluorophenoxy)-phenyl]-butan-3-ol,

1-(1-imidazolyl)-3-[4-(2,4-dichlorophenoxy)-phenyl]-butan-3-ol,

n_(D) ²⁰ 1.5972, and

1-(1-imidazolyl)-3-[4-(2,4-dibromophenoxy)-phenyl]-butan-3-ol.

EXAMPLE 35

2.26 g of 3-p-biphenylybutan-1-ol are dissolved in 10 ml ofisopropylamine and, after adding 0.5 g of Raney nickel, the solution isshaken for 15 hours at 160° in a tube. After cooling, filtering off thecatalyst and evaporating, 1-isopropylamino-3-p-biphenylyl-butane isobtained.

EXAMPLE 36

3.48 g of 1-bis-(2-hydroxyethyl)-3-(4'-chloro-4-biphenylyl)-butane[obtainable from 1-chloro-3-(4'-chloro-4-biphenylyl)-butane anddiethanolamine] are dissolved in 100 ml of xylene, 2 drops of H₂ SO₄ areadded and the mixture is boiled for an hour. After cooling and workingup in the customary manner,1-morpholino-3-(4'-chloro-4-biphenylyl)butane, m.p. 77° - 79°, isobtained.

EXAMPLE 37

0.1 g of p-toluenesulfonic acid is added to a solution of 3.48 g of1-bis-(2-hydroxyethyl)-3-(4'-chloro-4-biphenylyl)-butane and 0.61 g of2-aminoethanol in 100 ml of toluene and the mixture is boiled for 2.5hours and cooled. After working up in the customary manner,1-[4-(2-hydroxyethyl)-piperazino]-3-(4'-chloro-4-biphenylyl)-butane isobtained.

EXAMPLE 38

3 ml of concentrated hydrochloric acid are added at 0° to 3.26 g of1-morpholino-3-(4'-amino-4-biphenylyl)-butan-3-ol [obtainable bynitrating 1-morpholino-3-(4-biphenylyl)-butan-3-ol and reducing theresulting 1-morpholino-3-(4'-nitro-4-biphenylyl)-butan-3-ol], and asolution of 1.4 g of NaNO₂ in 6 ml of water is then added at 0°, whilestirring. After adding a solution of 0.7 g of boric acid in 1.5 g of 60%hydrofluoric acid, the mixture is stirred for 40 minutes and the productis filtered off, washed with water, methanol and ether and dried. Theresulting diazonium salt is heated at about 150° until decomposition iscomplete. This gives 1-morpholino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol.

EXAMPLE 39

3.26 g of 1-morpholino-3-(4'-amino-4-biphenylyl-butan-3-ol are dissolvedin 30 ml of 10% hydrochloric acid, 0.7 g of NaNO₂ in 2 ml of water isadded at 0° to 5°, the resulting diazonium salt solution is addeddropwise, slowly, to a hot solution of Cu₂ Cl₂ (obtained by reducing 2.1g of copper sulfate with SO₂ in 13 ml of water, in the presence of 2.6 gof NaCl), and the mixture is heated to 90° to 95° for a further 30minutes, cooled and worked up in the customary manner to give1-morpholino-3-(4'-chloro-4-biphenylyl)-butan-3-ol, m.p. 106° - 108°.

EXAMPLE 40

1-morpholino-3-(4'-bromo-4-biphenylyl)-butan-3-ol, m.p. 97° - 99°, isobtained analogously to Example 39 using Cu₂ Br₂ (instead of Cu₂ Cl₂).

EXAMPLE 41

A mixture of 2.22 g of p-iodofluorobenzene and 2.71 g of the sodium saltof 1-piperidino-4-p-hydroxyphenyl-butan-3-ol (obtainable by reactingp-hydroxyacetophenone with bromoacetic acid ethyl ester and zinc,reducing the resulting 3-p-hydroxyphenyl-3-hydroxybutyric acid ethylester by means of LiAlH₄ to give 3-p-hydroxyphenyl-butane-1,3-diolreaction with SOCl₂ to give 1-chloro-3-p-hydroxyphenyl-butan-3-ol andreaction with iperidine) is warmed to 90° for 8 hours in the presence of1 g of copper powder in 10 ml of HMPT and is then worked up in thecustomary manner. This gives1-piperidino-4-(4-p-fluorophenoxyphenyl)-butan-3-ol.

EXAMPLE 42

A solution of 3.59 g of 1-piperidino-4-p-iodophenyl-butan-3-ol(obtainable by reacting 1-chloro-3-p-iodophenyl-butan-3-ol withpiperidine) and 1.51 g of sodium p-chlorophenolate in 20 ml of DMF isheated at 130° for 8 hours. After working up in the customary manner,1-piperidino-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol, m.p. 73° - 75°, isobtained.

EXAMPLE 43

25.9 g of 3-(4'-fluoro-4-biphenylyl)-3-hydroxybutylaminep-toluenesulfonate are boiled with 1 g of p-toluenesulfonic acid in 500ml of toluene for 2 hours under a water separator, and the mixture iscooled and worked up with sodium hydroxide solution to give3-(4'-fluoro-4-biphenylyl)-2-buten-1-yl-amine.

The following are obtained analogously by dehydrating the correspondinghydroxyamines using p-toluenesulfonic acid:

1-Methylamino-3-p-biphenylyl-2-butene,

1-methylamino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-methylamino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-methylamino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-ethylamino-3-p-biphenylyl-2-butene,

1-ethylamino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-ethylamino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-ethylamino-3-(4-p-chlorophenoxy-phenyl)-2-buene,

1-n-propylamino-3-p-biphenylyl-2-butene,

1-n-propylamino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-n-propylamino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-n-propylamino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-isopropylamino-3-p-biphenylyl-2-butene,

1-isopropylamino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-isopropylamino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-isopropylamino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-n-butylamino-3-p-biphenylyl-2-butene,

1-n-butylamino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-n-butylamino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-n-butylamino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-isobutylamino-3-p-biphenylyl-2-butene,

1-isobutylamino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-isobutylamino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-isobutylamino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-sec.-butylamino-3-p-biphenylyl-2-butene,

1-sec.-butylamino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-sec.-butylamino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-sec.-butylamino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-tert.-butylamino-3-p-biphenylyl-2-butene,

1-tert.-butylamino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-tert.-butylamino-3-(4'-chloro-4-biphenylyl)-2-butene and

1-tert.-butylamino-3-(4-p-chlorophenoxy-phenyl)-2-butene.

EXAMPLE 44

A mixture of 3.1 g of 1-morpholino-3-biphenylyl-butan-3-ol, 0.1 g ofbenzenesulfonic acid and 80 ml of benzene is boiled for 24 hours under awater separator. After working up in the customary manner,1-morpholino-3-p-biphenylyl-2-butene is obtained.

The following are obtained analogously by dehydrating the correspondinghydroxyamines:

1-Morpholino-3-(2'-fluoro-4-biphenylyl)-2-butene,

1-morpholino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-morpholino-3-(2'-chloro-4-biphenylyl)-2-butene,

1-morpholino-3-(4'-chloro-4-biphenylyl)-2-butene, m.p. 109°-111°,

1-morpholino-3-(2'-bromo-4-biphenylyl)-2-butene,

1-morpholino-3-(4'-bromo-4-biphenylyl)-2-butene,

1-morpholino-3-(2',4'-difluoro-4-biphenylyl)-2-butene,

1-morpholino-3-(2',4'-dichloro-4-biphenylyl)-2-butene,

1-morpholino-3-(2',4'-dibromo-4-biphenylyl)-2-butene,

1-morpholino-3-p-phenoxy-phenyl-2-butene,

1-morpholino-3-(4-o-fluorophenoxy-phenyl)-2-butene,

1-morpholino-3-(4-p-fluorophenoxy-phenyl)-2-butene,

1-morpholino-3-(4-o-chlorophenoxy-phenyl)-2-butene,

1-morpholino-3-(4-p-chlorophenoxy-phenyl)-2-butene, m.p. 95°-97°,

1-morpholino-3-(4-o-bromophenoxy-phenyl)-2-butene,

1-morpholino-3-(4-p-bromophenoxy-phenyl)-2-butene,

1-morpholino-3-[4-(2,4-difluorophenoxy)-phenyl]-2-butene,

1-morpholino-3-[4-(2,4-dichlorophenoxy)-phenyl]-2-butene,

1-morpholino-3-[4-(2,4-dibromophenoxy)-phenyl]-2-butene,

1-morpholino-4-p-biphenylyl-3-pentene,

1-morpholino-(4'-fluoro-4-biphenylyl)-3-pentene,

1-morpholino-(4'-chloro-4-biphenylyl)-3-pentene,

1-morpholino-(4'-bromo-4-biphenylyl)-3-pentene,

1-morpholino-(4-p-chlorophenoxy-phenyl)-3-pentene,

1-pyrrolidino-3-p-biphenylyl-2-butene,

1-pyrrolidino-3-(2'-fluoro-4-biphenylyl)-2-butene,

1-pyrrolidino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-pyrrolidino-3-(2'-chloro-4-biphenylyl)-2-butene,

1-pyrrolidino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-pyrrolidino-3-(2'-bromo-4-biphenylyl)-2-butene,

1-pyrrolidino-3-(4'-bromo-4-biphenylyl)-2-butene,

1-pyrrolidino-3-(2',4'-difluoro-4biphenylyl)-2-butene,

1-pyrrolidino-3-(2',4'-dichloro-4-biphenylyl)-2-butene,

1-pyrrolidino-3-(2',4'-dibromo-4-biphenylyl)-2-butene,

1-pyrrolidino-3-p-phenoxy-phenyl-2-butene,

1-pyrrolidino-3-(4-o-fluorophenoxy-phenyl)-2-butene,

1-pyrrolidino-3-(4-p-fluorophenoxy-phenyl)-2-butene,

1-pyrrolidino-3-(4-o-chlorophenoxy-phenyl)-2-butene,

1-pyrrolidino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-pyrrolidino-3-(4-o-bromophenoxy-phenyl)-2-butene,

1-pyrrolidino-3-(4-p-bromophenoxy-phenyl)-2-butene,

1-pyrrolidino-3-[4-(2,4-difluorophenoxy)-phenyl]-2-butene,

1-pyrrolidino-3-[4-(2,4-dichlorophenoxy)-phenyl]-2-butene,

1-pyrrolidino-3-[4-(2,4-dibromophenoxy)-phenyl]-2-butene,

1-piperidino-3-p-biphenylyl-2-butene,

1-piperidino-3-(2'-fluoro-4-biphenylyl)-2-butene,

1-piperidino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-piperidino-3-(2'-chloro-4-biphenylyl)-2-butene,

1-piperidino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-piperidino-3-(2'-bromo-4-biphenylyl)-2-butene,

1-piperidino-3-(4'-bromo-4-biphenylyl)-2-butene, m.p. 130°-132°,

1-piperidino-3-(2',4'-difluoro-4-biphenylyl)-2-butene,

1-piperidino-3-(2',4'-dichloro-4-biphenylyl)-2-butene,

1-piperidino-3-(2',4'-dibromo-4-biphenylyl)-2-butene,

1-piperidino-3-p-phenoxy-phenyl-2-butene,

1-piperidino-3-(4-o-fluorophenoxy-phenyl)-2-butene,

1-piperidino-3-(4-p-fluorophenoxy-phenyl)-2-butene,

1-piperidino-3-(4-o-chlorophenoxy-phenyl)-2-butene,

1-piperidino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-piperidino-3-(4-o-bromophenoxy-phenyl)-2-butene,

1-piperidino-3-(4-p-bromophenoxy-phenyl)-2-butene,

1-piperidino-3-[4-(2,4-difluorophenoxy)-phenyl]-2-butene,

1-piperidino-3-[4-(2,4-dichlorophenoxy)-phenyl]-2-butene,

1-piperidino-3-[4-(2,4-dibromophenoxy)-phenyl]-2-butene,

1-piperidino-4-p-biphenylyl-3-pentene,

1-piperidino-4-(4'-fluoro-4-biphenylyl)-3-pentene,

1-piperidino-4-(4'-chloro-4-biphenylyl)-3-pentene,

1-piperidino-4-(4'-bromo-4-biphenylyl)-3-pentene,

1-piperidino-4-(4-p-chlorophenoxy-phenyl)-3-pentene,

1-(4-methylpiperidino)-3-p-biphenylyl-2-butene,

1-(4-methylpiperidino)-3-(2'-fluoro-4-biphenylyl)-2-butene,

1-(4-methylpiperidino)-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-(4-methylpiperidino)-3-(2'-chloro-4-biphenylyl)-2-butene,

1-(4-methylpiperidino)-3-(4'-chloro-4-biphenylyl)-2-butene,

1-(4-methylpiperidino)-3-(2'-bromo-4-biphenylyl)-2-butene,

1-(4-methylpiperidino)-3-(4'-bromo-4-biphenylyl)-2-butene,

1-(4-methylpiperidino)-3-(2',4'-difluoro-4-biphenylyl)-2-butene,

1-(4-methylpiperidino)-3-(2',4'-dichloro-4-biphenylyl)-2-butene,

1-(4-methylpiperidino)-3-(2',4'-dibromo-4-biphenylyl)-2-butene,

1-(4-methylpiperidino)-3-p-phenoxy-phenyl-2-butene,

1-(4methylpiperidino)-3-(4-o-fluorophenoxy-phenyl)-2-butene,

1-(4-methylpiperidino)-3-(4-p-fluorophenoxy-phenyl)-2-butene,

1-(4-methylpiperidino)-3-(4-o-chlorophenoxy-phenyl)-2-butene,

1-(4-methylpiperidino)-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-(4-methylpiperidino)-3-(4-o-bromophenoxy-phenyl)-2-butene,

1-(4-methylpiperidino)-3-(4-p-bromophenoxy-phenyl)-2-butene,

1-(4-methylpiperidino)-3-[4-(2,4-difluorophenoxy)-phenyl]-2-butene,

1-(4-methylpiperidino)-3-[4-(2,4-dichlorophenoxy)-phenyl]-2-butene,

1-(4-methylpiperidino)-3-[4-(2,4-dibromophenoxy)-phenyl]-2-butene,

1-homopiperidino-3-p-biphenylyl-2-butene,

1-homopiperidino-3-(2'-fluoro-4-biphenylyl)-2-butene,

1-homopiperidino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-homopiperidino-3-(2'-chloro-4-biphenylyl)-2-butene,

1-homopiperidino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-homopiperidino-3-(2'-bromo-4-biphenylyl)-2-butene,

1-homopiperidino-3-(4'-bromo-4-biphenylyl)-2-butene,

1-homopiperidino-3-(2',4'-difluoro-4-biphenylyl)-2-butene,

1-homopiperidino-3-(2',4'-dichloro-4-biphenylyl)-2-butene,

1-homopiperidino-3-(2',4'-dibromo-4-biphenylyl)-2-butene,

1-homopiperidino-3-p-phenoxy-phenyl-2-butene,

1-homopiperidino-3-(4-o-fluorophenoxy-phenyl)-2-butene,

1-homopiperidino-3-(4-p-fluorophenoxy-phenyl)-2-butene,

1-homopiperidino-3-(4-o-chlorophenoxy-phenyl)-2-butene,

1-homopiperidino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-homopiperidino-3-(4-o-bromophenoxy-phenyl)-2-butene,

1-homopiperidino-3-(4-p-bromophenoxy-phenyl)-2-butene,

1-homopiperidino-3-[4-(2,4-difluorophenoxy)-phenyl]-2-butene,

1-homopiperidino-3-[4-(2,4-dichlorophenoxy)-phenyl]-2-butene,

1-homopiperidino-3-[4-(2,4-dibromophenoxy)-phenyl]-2-butene,

1-piperazino-3-p-biphenylyl-2-butene,

1-piperidino-3-(2'-fluoro-4-biphenylyl)-2-butene,

1-piperazino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-piperazino-3-(2'-chloro-4-biphenylyl)-2-butene,

1-piperazino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-piperazino-3-(2'-bromo-4-biphenylyl)-2-butene,

1-piperazino-3-(4'-bromo-4-biphenylyl)-2-butene,

1-piperazino-3-(2',4'-difluoro-4-biphenylyl)-2-butene,

1-piperazino-3-(2',4'-dichloro-4-biphenylyl)-2-butene,

1-piperazino-3-(2',4'-dibromo-4-biphenylyl)-2-butene,

1-piperazino-3-p-phenoxy-phenyl-2-butene,

1-piperazino-3-(4-o-fluorophenoxy-phenyl)-2-butene,

1-piperazino-3-(4-p-fluorophenoxy-phenyl)-2-butene,

1-piperazino-3-(4-o-chlorophenoxy-phenyl)-2-butene,

1-piperazino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-piperazino-3-(4-o-bromophenoxy-phenyl)-2-butene,

1-piperazino-3-(4-p-bromophenoxy-phenyl)-2-butene,

1-piperazino-3-[4-(2,4-difluorophenoxy)-phenyl]-2-butene,

1-piperazino-3-[4-(2,4-dichlorophenoxy)-phenyl]-2-butene,

1-piperazino-3-[4-(2,4-dibromophenoxy)-phenyl]-2-butene,

1-diethylamino-3-p-biphenylyl-2-butene,

1-diethylamino-3-(2'-fluoro-4-biphenylyl)-2-butene,

1-diethylamino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-diethylamino-3-(2'-chloro-4-biphenylyl)-2-butene,

1-diethylamino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-diethylamino-3-(2'-bromo-4-biphenylyl)-2-butene,

1-diethylamino-3-(4'-bromo-4-biphenylyl)-2-butene,

1-diethylamino-3-(2',4'-difluoro-4-biphenylyl)-2-butene,

1-diethylamino-3-(2',4'-dichloro-4-biphenylyl)-2-butene,

1-diethylamino-3-(2',4'-dibromo-4-biphenylyl)-2-butene,

1-diethylamino-3-p-phenoxy-phenyl-2-butene,

1-diethylamino-3-(4-o-fluorophenoxy-phenyl)-2-butene,

1-diethylamino-3-(4-p-fluorophenoxy-phenyl)-2-butene,

1-diethylamino-3-(4-o-chlorophenoxy-phenyl)-2-butene,

1-diethylamino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-diethylamino-3-(4o-bromophenoxy-phenyl)-2-butene,

1-diethylamino-3-(4-p-bromophenoxy-phenyl)-2-butene,

1-diethylamino-3-[4-(2,4-difluorophenoxy)-phenyl]-2-butene,

1-diethylamino-3-[4-(2,4-dichlorophenoxy)-phenyl]-2-butene,

1-diethylamino-3-[4-(2,4-dibromophenoxy)-phenyl]-2-butene,

1-phthalimido-3-p-biphenylyl-2-butene,

1-phthalimido-3-(2'-fluoro-4-biphenylyl)-2-butene,

1-phthalimido-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-phthalimido-3-(2'-chloro-4-biphenylyl)-2-butene,

1-phthalimido-3-(4'-chloro-4-biphenylyl)-2-butene, m.p. 188° - 191°,

1-phthalimido-3-(2'-bromo-4-biphenylyl)-2-butene,

1-phthalimido-3-(4'-bromo-4-biphenylyl)-2-butene,

1-phthalimido-3-(2',4'-difluoro-4-biphenylyl)-2-butene,

1-phthalimido-3-(2',4'-dichloro-4-biphenylyl)-2-butene,

1-phthalimido-3-(2',4'-dibromo-4-biphenylyl)-2-butene,

1-phthalimido-3-p-phenoxy-phenyl-2-butene,

1-phthalimido-3-(4-o-fluorophenoxy-phenyl)-2-butene,

1-phthalimido-3-(4-p-fluorophenoxy-phenyl)-2-butene,

1-phthalimido-3-(4-o-chlorophenoxy-phenyl)-2-butene,

1-phthalimido-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-phthalimido-3-(4-o-bromophenoxy-phenyl)-2-butene,

1-phthalimido-3-(4-p-bromophenoxy-phenyl)-2-butene,

1-phthalimido-3-[4-(2,4-difluorophenoxy)-phenyl]-2-butene,

1-phthalimido-3-[4-(2,4-dichlorophenoxy)-phenyl]-2-butene,

1-phthalimido-3-[4-(2,4-dibromophenoxy)-phenyl]-2-butene,

1-(1-imidazolyl)-3-p-biphenylyl-2-butene,

1-(1-imidazolyl)-3-(2'-fluoro-4-biphenylyl)-2-butene,

1-(1-imidazolyl)-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-(1-imidazolyl)-3-(2'-chloro-4-biphenylyl)-2-butene,

1-(1-imidazolyl)-3-(4'-chloro-4-biphenylyl)-2-butene,

1-(1-imidazolyl)-3-(2'-bromo-4-biphenylyl)-2-butene,

1-(1-imidazolyl)-3-(4'-bromo-4-biphenylyl)-2-butene,

1-(1-imidazolyl)-3-(2',4'-difluoro-4-biphenylyl)-2-butene,

1-(1-imidazolyl)-3-(2',4'-dichloro-4-biphenylyl)-2-butene,

1-(1-imidazolyl)-3-(2',4'-dibromo-4-biphenylyl)-2-butene,

1-(1-imidazolyl)-3-p-phenoxy-phenyl-2-butene,

1-(1-imidazolyl)-3-(4-o-fluorophenoxy-phenyl)-2-butene,

1-(1-imidazolyl)-3-(4-p-fluorophenoxy-phenyl)-2-butene,

1-(1-imidazolyl)-3-(4-o-chlorophenoxy-phenyl)-2-butene,

1-(1-imidazolyl)-3-(4-p-chlorophenoxy-phenyl)-2-butene, m.p. 79°-81°,

1-(1-imidazolyl)-3-(4-o-bromophenoxy-phenyl)-2-butene,

1-(1-imidazolyl)-3-(4-p-bromophenoxy-phenyl)-2-butene,

1-(1-imidazolyl)-3-[4-(2,4-difluorophenoxy)-phenyl]-2-butene,

1-(1-imidazolyl)-3-[4-(2,4-dichlorophenoxy)-phenyl]-2-butene n_(D) ²⁰1.5671, and

1-(1-imidazolyl)-3-[4-(2,4-dibromophenoxy)-phenyl]-2-butene.

EXAMPLE 45

The following are obtained analogously to Example 44 by dehydrating thecorresponding hydroxyamines:

1-Di-n-propylamino-3-p-biphenylyl-2-butene,

1-di-n-propylamino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-di-n-propylamino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-di-n-propylamino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-diisopropylamino-3-p-biphenylyl-2-butene,

1-diisopropylamino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-diisopropylamino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-diisopropylamino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-di-n-butylamino-3-p-biphenylyl-2-butene,

1-di-n-butylamino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-di-n-butylamino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-di-n-butylamino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-diisobutylamino-3-p-biphenylyl-2-butene,

1-diisobutylamino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-diisobutylamino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-diisobutylamino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-di-n-pentylamino-3-p-biphenylyl-2-butene,

1-di-n-pentylamino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-di-n-pentylamino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-di-n-pentylamino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-di-n-hexylamino-3-p-biphenylyl-2-butene,

1-di-n-hexylamino-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-di-n-hexylamino-3-(4'-chloro-4-biphenylyl)-2-butene,

1-di-n-hexylamino-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-(2-dimethylamino-ethylamino)-3-p-biphenylyl-2-butene,

1-(2-dimethylamino-ethylamino)-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-(2-dimethylamino-ethylamino)-3-(4'-chloro-4-biphenylyl)-2-butene,

1-(2-dimethylamino-ethylamino)-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-(2-diethylamino-ethylamino)-3-p-biphenylyl-2-butene,

1-(2-diethylamino-ethylamino)-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-(2-diethylamino-ethylamino)-3-(4'-chloro-4-biphenylyl)-2-butene,

1-(2-diethylamino-ethylamino)-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-(3-dimethylamino-propylamino)-3-p-biphenylyl-2-butene,

1-(3-dimethylamino-propylamino)-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-(3-dimethylamino-propylamino)-3-(4'-chloro-4-biphenylyl)-2-butene,

1-(3-dimethylamino-propylamino)-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-(2-methylpiperidino)- 3-p-biphenylyl-2-butene,

1-(2-methylpiperidino)-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-(2-methylpiperidino)-3-(4'-chloro:4-biphenylyl)-2-butene,

1-(2-methylpiperidino)-3-(4-p-chlorphenoxy-phenyl)-2-butene,

1-(3-methylpiperidino)-3-p-biphenylyl-2-butene,

1-(3-methylpiperidino)-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-(3-methylpiperidino)-3-(4'-chloro-4-biphenylyl)-2-butene,

1-(3-methylpiperidino)-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-(2,6-dimethylpiperidino)-3-p-biphenylyl-2-butene,

1-(2,6-dimethylpiperidino)-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-(2,6-dimethylpiperidino)- 3-(4'-chloro-4-biphenylyl)-2-butene,

1-(2,6-dimethylpiperidino)-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-(4-methyl-piperazino)-3-p-biphenylyl-2-butene,

1-(4-methyl-piperazino)-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-(4-methyl-piperazino)-3-(4'-chloro-4-biphenylyl)-2-butene,

1-(4-methyl-piperazino)-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-(4-ethyl-piperazino)-3-p-biphenylyl-2-butene,

1-(4-ethyl-piperazino)-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-(4-ethyl-piperazino)-3-(4'-chloro-4-biphenylyl)-2-butene,

1-(4-ethyl-piperazino)-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-(4-n-hexyl-piperazino)-3-p-biphenylyl-2-butene,

1-(4-n-hexyl-piperazino)-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-(4-n-hexyl-piperazino)-3-(4'-chloro-4-biphenylyl)-2-butene,

1-(4-n-hexyl-piperazino)-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-[4-(2-hydroxyethyl)-piperazino]-3-p-biphenylyl-2-butene,

1-[4-(2-hydroxyethyl)-piperazino]-3-(4'-fluoro-4-biphenylyl)-2-butene,

1-[4-(2-hydroxyethyl)-piperazino]-3-(4'-chloro-4-biphenylyl)-2-buteneand

1[4-(2-hydroxyethyl)-piperazino]-3-(4-p-chlorophenoxy-phenyl)-2-butene.

EXAMPLE 46

A mixture of 1 g of 3-(4'-chloro-4-biphenylyl)-3-hydroxy-butylamine, 2.5ml of a 67% solution of HI in acetic acid and 5 ml of acetic acid isboiled for 90 minutes, evaporated and worked up using water andchloroform. This gives 3-(4'-chloro-4-biphenylyl)-butylamine hydriodide,which is converted into the free base employing a sodium hydroxidesolution. Tartrate, m.p. 200° - 202°.

The following are obtained analogously from the correspondinghydroxyamines, using HI/acetic acid:

1 -Methylamino-3-p-biphenylyl-butane,

1-methylamino-3-(4'-fluoro-4-biphenylyl)-butane,

1-methylamino-3-(4'-chloro-4-biphenylyl)-butane,

1-methylamino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-ethylamino-3-p-biphenylyl-butane,

1-ethylamino-3-(4'-fluoro-4-biphenylyl)-butane,

1- ethylamino-3-(4'-chloro-4-biphenylyl)-butane,

1-ethylamino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-n-propylamino-3-p-biphenylyl-butane,

1-n-propylamino-3-(4'-fluoro-4-biphenylyl)-butane,

1-n-propylamino-3-(4'-chloro-4-biphenylyl)-butane,

1-n-propylamino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-isopropylamino-3-p-biphenylyl-butane,

1-isopropylamino-3-(4'-fluoro-4-biphenylyl)-butane,

1-isopropylamino-3-(4'-chloro-4-biphenyl)-butane,

1-isopropylamino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-n-butylamino-3-p-biphenylyl-butane,

1-n-butylamino-3-(4'-fluoro-4-biphenylyl)-butane,

1-n-butylamino-3-(4'-chloro-4biphenylyl)-butane,

1-n-butylamino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-isobutylamino-3-p-biphenylyl-butane,

1-isobutylamino-3-(4'-fluoro-4-biphenylyl)-butane,

1-isobutylamino-3-(4'-chloro-4-biphenylyl)-butane,

1-isobutylamino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-sec.-butylamino-3-p-biphenylyl-butane,

1-sec.-butylamino-3-(4'-fluoro-4-biphenylyl)-butane,

1-sec.-butylamino-3-(4'-chloro-4-biphenylyl)-butane,

1-sec.-butylamino-3-(4 -p-chlorophenoxy-phenyl)-butane,

1-tert.-butylamino-3-p-biphenylyl-butane,

1-tert.-butylamino-3-(4'-fluoro-4-biphenylyl)-butane,

1-tert.-butylamino-3-(4'-chloro-4-biphenylyl)-butane and

1-tert.-butylamino-3-(4-p-chlorophenoxy-phenyl)-butane.

EXAMPLE 47

A mixture of 3.1 g of 1-morpholino-3-p-biphenylyl-butan-3-ol, 10 ml of67% hydriodic acid and 18 ml of acetic acid is heated at 150° for 1.5hours. 1-Morpholino-3-p-biphenylyl-butane is obtained after cooling andworking up in the customary manner.

The following are obtained analogously by reducing the correspondinghydroxyamines:

1-Morpholino-2-p-biphenylyl-propane,

1-morpholino-2-(4'-fluoro-4-biphenylyl)-propane,

1-morpholino-2-(4'-chloro-4-biphenylyl)-propane,

1-morpholino-2-(4'-bromo-4-biphenylyl)-propane,

1-morpholino-2-(4-p-chlorophenoxy-phenyl)-propane,

1-morpholino-3-(2'-fluoro-4-biphenylyl)-butane,

1-morpholino-3-(4'-fluoro-4-biphenylyl)-butane, m.p. 54° - 56°,

1-morpholino-3-(2'-chloro-4-biphenylyl)-butane,

1-morpholino-3-(4'-chloro-4-biphenylyl)-butane, m.p. 77° - 79°,

1-morpholino-3-(2'-bromo-4-biphenylyl)-butane,

1-morpholino-3-(4'-bromo-4-biphenyl)-butane,

1-morpholino-3-(2',4'-difluoro-4-biphenylyl)-butane, hydrochloride, m.p.198° -200°,

1-morpholino-3-(2',4'-dichloro-4-biphenylyl)-butane,

1-morpholino-3-(2',4'-dibromo-4-biphenylyl)-butane,

1-morpholino-3-p-phenoxy-phenyl-butane,

1-morpholino-3-(4-o-fluorophenoxy-phenyl)-butane,

1-morpholino-3-(4-p-fluorophenoxy-phenyl)-butane,

1-morpholino-3-(4-o-chlorophenoxy-phenyl)-butane,

1-morpholino-3-(4-p-chlorophenoxy-phenyl)-butane, hydrochloride, m.p.172° - 174°,

1-morpholino-3-(4-o-bromophenoxy-phenyl)-butane,

1-morpholino-3-(4-p-bromophenoxy-phenyl)-butane,

1-morpholino-3-[4-(2,4-difluorophenoxy)-phenyl]-butane,

1-morpholino-3-[4-(2,4-dichlorophenoxy)-phenyl]-butane,

1-morpholino-3-[4-(2,4-dibromophenoxy)-phenyl]-butane,

1-morpholino-4-p-biphenylyl-pentane,

1-morpholino-4-(4'-fluoro-4-biphenylyl)-pentane,

1-morpholino-4-(4'-chloro-4-biphenylyl)-pentane,

1-morpholino-4-(4'-bromo-4-biphenylyl)-pentane,

1-morpholino-4-(4-p-chlorophenoxy-phenyl)-pentane,

1-pyrrolidino-3-p-biphenylyl-butane,

1-pyrrolidino-3-(2'-fluoro-4-biphenylyl)-butane,

1-pyrrolidino-3-(4'-fluoro-4-biphenylyl)-butane,

1-pyrrolidino-3-(2'-chloro-4-biphenylyl)-butane,

1-pyrrolidino-3-(4'-chloro-4-biphenylyl)-butane,

1-pyrrolidino-3-(2'-bromo-4-biphenylyl)-butane,

1-pyrrolidino-3-(4'-bromo-4-biphenylyl)-butane,

1-pyrrolidino-3-(2',4'-difluoro-4-biphenylyl)-butane,

1-pyrrolidino-3-(2',4'-dichloro-4-biphenylyl)-butane,

1-pyrrolidino-3-(2',4'-dibromo-4-biphenylyl)-butane,

1-pyrrolidino-3-p-phenoxy-phenyl-butane,

1-pyrrolidino-3-(4-o-fluorophenoxy-phenyl)-butane,

1-pyrrolidino-3-(4-p-fluorophenoxy-phenyl)-butane,

1-pyrrolidino-3-(4-o-chlorophenoxy-phenyl)-butane,

1-pyrrolidino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-pyrrolidino-3-(4-o-bromophenoxy-phenyl)-butane,

1-pyrrolidino-3-(4-p-bromophenoxy-phenyl)-butane,

1-pyrrolidino-3-[4-(2,4-difluorophenoxy)-phenyl]-butane,

1-pyrrolidino-3-[4-(2,4-dichlorophenoxy)-phenyl]-butane,

1-pyrrolidino-3-[4-(2,4-dibroophenoxy)-phenyl]-butane,

1-piperidino-2-p-biphenylyl-propane,

1-piperidino-2-(4'-fluoro-4-biphenylyl)-propane,

1-piperidino-2-(4'-chloro-4-biphenylyl)-propane,

1-piperidino-2-(4'-bromo-4-biphenylyl)-propane, hydrochloride, m.p.260° - 261°,

1-piperidino-2-(4-p-chlorophenoxy-phenyl)-propane,

1-piperidino-3-p-biphenylyl-butane,

1-piperidino-3-(4'-fluoro-4-biphenylyl)-butane, hydrochloride, m.p.207° - 209°,

1-piperidino-3-(2'-chloro-4-biphenylyl)-butane,

1-piperidino-3-(4'-chloro-4-biphenylyl)-butane, hydrochloride, m.p.215°,

1-piperidino-3-(2'-bromo-4-biphenylyl)-butane,

1-piperidino-3-(4'-bromo-4-biphenylyl)-butane,

1-piperidino-3-(2',4'-difluoro-4-biphenylyl)-butane,

1-piperidino-3-(2',4'-dichloro-4-biphenylyl)-butane,

1-piperidino-3(2',4'-dibromo-4-biphenylyl)-butane,

1-piperidino-3-p-phenoxy-phenyl-butane,

1-piperidino-3-(4-o-fluorophenoxy-phenyl)-butane,

1-piperidino-3-(4-p-fluorophenoxy-phenyl)-butane,

1-piperidino-3-(4-o-chlorophenoxy-phenyl)-butane,

1-piperidino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-piperidino-3-(4-o-bromophenoxy-phenyl)-butane,

1-piperidino-3-(4-p-bromophenoxy-phenyl)-butane,

1-piperidino-3-[4-(2,4-difluorophenoxy)-phenyl]-butane,

1-piperidino-3-[4-(2,4-dichlorophenoxy)-phenyl]-butane,

1-piperidino-3-[4-(2,4-dibromophenoxy)-phenyl]-butane,

1 -piperidino-4-p-biphenylyl-pentane,

1-piperidino-4-(4'-fluoro-4-biphenylyl)-pentane,

1-piperidino-4-(4'-chloro-4-biphenylyl)-pentane,

1-piperidino-4-(4'-bromo-4-biphenylyl)-pentane, hydrochloride, m.p.235°; hydriodide, m.p. 212° - 214°,

1-piperidino-4-(4-p-chlorophenoxy-phenyl)-pentane,

1-(4-methylpiperidino)-3-p-biphenylyl-butane,

1-(4-methylpiperidino)-3-(2'-fluoro-4-biphenylyl)-butane,

1-(4-methylpiperidino)-3-(4'-fluoro-4-biphenylyl)-butane,

1-(4-methylpiperidino)-3-(2'-chloro-4-biphenylyl)-butane,

1-(4-methylpiperidino)-3-(4'-chloro-4-biphenylyl)-butane,

1-(4-methylpiperidino)-3-(2'-bromo-4-biphenylyl)-butane,

1-(4-methylpiperidino)-3-(4'-bromo-4-biphenylyl)-butane,

1-(4-methylpiperidino)-3-(2',4'-difluoro-4-biphenylyl)-butane,

1-(4-methylpiperidino)-3-(2',4'-dichloro-4-biphenylyl)-butane,

1-(4-methylpiperidino)-3-(2',4'-dibromo-4-biphenylyl)-butane,

1-(4-methylpiperidino)-3-p-phenoxy-phenyl-butane,

1-(4-methylpiperidino)-3-(4-o-fluorophenoxy-phenyl)-butane,

1-(4-methylpiperidino)-3-(4-p-fluorophenoxy-phenyl)-butane,

1-(4-methylpiperidino)-3-(4-o-chlorophenoxy-phenyl)-butane,

1-(4-methylpiperidino)-3-(4-p-chlorophenoxy-phenyl)-butane,

1-(4-methylpiperidino)-3-(4 -o-bromophenoxy-phenyl)-butane

1-(4-methylpiperidino)-3-(4-p-bromophenoxy-phenyl)-butane,

1-(4-methylpiperidino)-3-[4-(2,4-difluorophenoxy)-phenyl]-butane,

1-(4-methylpiperidino)-3-[4-(2,4-dichlorophenoxy)-phenyl]-butane,

1-(4-methylpiperidino)-3-[4-(2,4-dibromophenoxy)-phenyl]-butane,

1-homopiperidino-3-p-biphenylyl-butane,

1-homopiperidino-3-(2'-fluoro-4-biphenylyl)-butane,

1-homopiperidino-3-(4'-fluoro-4-biphenylyl)-butane,

1-homopiperidino-3-(2'-chloro-4-biphenylyl)-butane,

1-homopiperidino-3-(4'-chloro-4-biphenylyl)-butane,

1-homopiperidino-3-(2'-bromo-4-biphenylyl)-butane,

1-homopiperidino-3 -(4'-bromo-4-biphenylyl)-butane,

1-homopiperidino-3-(2',4'-difluoro-4-biphenylyl)-butane,

1-homopiperidino-3-(2' ,4'-dichloro-4-biphenylyl)-butane,

1-homopiperidino-3-(2',4'-dibromo-4-biphenylyl)-butane,

1-homopiperidino-3-p-phenoxy-phenyl-butane,

1-homopiperidino-3-(4-o-fluorophenoxy-phenyl)-butane,

1-homopiperidino-3-(4-p-fluorophenoxy-phenyl)-butane,

1-homopiperidino-3-(4-o-chlorophenoxy-phenyl)-butane,

1-homopiperidino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-homopiperidino-3-(4-o-bromophenoxy-phenyl)-butane,

1-homopiperidino-3-(4-p-bromophenoxy-phenyl)-butane,

1-homopiperidino-3-[4-(2,4-difluorophenoxy)-phenyl]-butane,

1-homopiperidino-3-[4-(2,4-dichlorophenoxy)-phenyl]-butane,

1-homopiperidino-3-[4-(2,4-dibromophenoxy)-phenyl]-butane,

1-piperazino-3-p-biphenylyl-butane,

1-piperazino-3-(2'-fluoro-4-biphenylyl)-butane,

1-piperazino-3-(4'-fluoro-4-biphenylyl)-butane, m.p. 67°-69°,

1-piperazino-3-(2'-chloro-4-biphenylyl)-butane,

1-piperazino-3-(4'-chloro-4-biphenylyl)-butane,

1-piperazino-3-(2'-bromo-4-biphenylyl)-butane,

1-piperazino-3-(4'-bromo-4-biphenylyl)-butane,

1-piperazino-3-(2',4'-difluoro-4-biphenylyl)-butane,

1-piperazino-3-(2',4'-dichloro-4-biphenylyl)-butane,

1-piperazino-3-(2',4'-dibromo-4-biphenylyl)-butane,

1-piperazino-3-p-phenoxy-phenyl-butane,

1-piperazino-3-(4-o-fluorophenoxy-phenyl)-butane,

1-piperazino-3-(4-p-fluorophenoxy-phenyl)-butane,

1-piperazino-3-(4-o-chlorophenoxy-phenyl)-butane,

1-piperazino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-piperazino-3-(4-o-bromophenoxy-phenyl)-butane,

1-piperazino-3-(4-p-bromophenoxy-phenyl)-butane,

1-piperazino-3-[4-(2,4-difluorophenoxy)-phenyl]-butane,

1-piperazino-3-[4-(2,4-dichlorophenoxy)-phenyl]-butane,

1-piperazino-3-[4-(2,4-dibromophenoxy)-phenyl]-butane,

1-diethylamino-3-p-biphenylyl-butane,

1-diethylamino-3-(2'-fluoro-4-biphenylyl)-butane,

1-diethylamino-3-(4'-fluoro-4-biphenylyl)-butane,

1-diethylamino-3-(2'-chloro-4-biphenylyl)-butane,

1-diethylamino-3-(4'-chloro-4-biphenylyl)-butane, m.p. 42°-44°, b.p.175°-180°/0.1 mm,

1-diethylamino-3-(2'-bromo-4-biphenylyl)-butane,

1-diethylamino-3-(4'-bromo-4-biphenylyl)-butane,

1-diethylamino-3-(2',4'-difluoro-4-biphenylyl)-butane,

1-diethylamino-3-(2',4'-dichloro-4-biphenylyl)-butane,

1-diethylamino-3-(2',4'-dibromo-4-biphenylyl)-butane,

1-diethylamino-3-p-phenoxy-phenyl-butane,

1-diethylamino-3-(4-o-fluorophenoxy-phenyl)-butane,

1-diethylamino-3-(4-p-fluorophenoxy-phenyl)-butane,

1-diethylamino-3-(4-o-chlorophenoxy-phenyl)-butane,

1-diethylamino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-diethylamino-3-(4-o-bromophenoxy-phenyl)-butane,

1-diethylamino-3-(4-p-bromophenoxy-phenyl)-butane,

1-diethylamino-3-[4-(2,4-difluorophenoxy)-phenyl]-butane,

1-diethylamino-3-[4-(2,4-dichlorophenoxy)-phenyl]-butane,

1-diethylamino-3-[4-(2,4-dibromophenoxy)-phenyl]-butane,

1-phthalimido-3-p-biphenylyl-butane, m.p. 120°-123°,

1-phthalimido-3-(2'-fluoro-4-biphenylyl)-butane, m.p. 75°-79°,

1-phthalimido-3-(4'-fluoro-4-biphenylyl)-butane, m.p. 142°-144°,

1-phthalimido-3-(2'-chloro-4-biphenylyl)-butane,

1-phthalimido-3-(4'-chloro-4-biphenylyl)-butane, m.p. 174°-176°,

1-phthalimido-3-(2'-bromo-4-biphenylyl)-butane,

1-phthalimido-3-(4'-bromo-4-biphenylyl)-butane, m.p. 180°-182°,

1-phthalimido-3-(2',4'-difluoro-4-biphenylyl)-butane, m.p. 95°-96°,

1-phthalimido-3-(2',4'-dichloro-4-biphenylyl)-butane,

1-phthalimido-3-(2',4'-dibromo-4-biphenylyl)-butane,

1-phthalimido-3-p-phenoxyphenyl-butane,

1-phthalimido-3-(4-o-fluorophenoxy-phenyl)-butane,

1-phthalimido-3-(4-p-fluorophenoxy-phenyl)-butane,

1-phthalimido-3-(4-o-chlorophenoxy-phenyl)-butane,

1-phthalimido-3-(4-p-chlorophenoxy-phenyl)-butane, m.p. 60°-62°,

1-phthalimido-3-(4-o-bromophenoxy-phenyl)-butane,

1-phthalimido-3-(4-p-bromophenoxy-phenyl)-butane,

1-phthalimido-3-[4-(2,4-difluorophenoxy)-phenyl]-butane,

1-phthalimido-3-[4-(2,4-dichlorophenoxy)-phenyl]-butane,

1-phthalimido-3-[4-(2,4-dibromophenoxy)-phenyl]-butane,

1-(1-imidazolyl)-3-p-biphenylyl-butane,

1-(1-imidazolyl)-3-(2'-fluoro-4-biphenylyl)-butane,

1-(1-imidazolyl)-3-(4'-fluoro-4-biphenylyl)-butane, m.p. 101°-103°,

1-(1-imidazolyl)-3-(2'-chloro-4-biphenylyl)-butane,

1-(1-imidazolyl)-3-(4'-chloro-4-biphenylyl)-butane, m.p. 129°-131°,

1-(1-imidazolyl)-3-(2'-bromo-4-biphenylyl)-butane,

1-(1-imidazolyl)-3-(4'-bromo-4-biphenylyl)-butane, hydrochloride, m.p.230°-232°,

1-(1-imidazolyl)-3-(2',4'-difluoro-4-biphenylyl)-butane, hydrochloride,m.p. 81°-83°,

1-(1-imidazolyl)-3-(2',4'-dichloro-4-biphenylyl)-butane,

1-(1-imidazolyl)-3-(2',4'-dibromo-4-biphenylyl)-butane,

1-(1-imidazolyl)-3-p-phenoxy-phenyl-butane,

1-(1-imidazolyl)-3-(4-o-fluorophenoxy-phenyl)-butane,

1-(1-imidazolyl)-3-(4-p-fluorophenoxy-phenyl)-butane,

1-(1-imidazolyl)-3-(4-o-chlorophenoxy-phenyl)-butane,

1-(1-imidazolyl)-3-(4-p-chlorophenoxy-phenyl)-butane, m.p. 66°-70°,

1-(1-imidazolyl)-3-(4-o-bromophenoxy-phenyl)-butane,

1-(1-imidazolyl)-3-(4-p-bromophenoxy-phenyl)-butane,

1-(1-imidazolyl)-3-[4-(2,4-difluorophenoxy)-phenyl]-butane,

1-(1-imidazolyl)-3-[4-(2,4-dichlorophenoxy)-phenyl]-butane and

1-(1-imidazolyl)-3-[4-(2,4-dibromophenoxy)-phenyl]-butane.

EXAMPLE 48

The following are obtained, analogously to Example 47, by reducing thecorresponding hydroxyamines, using HI:

1-di-n-propylamino-3-p-biphenylyl-butane,

1-di-n-propylamino-3-(4'-fluoro-4-biphenylyl)-butane,

1-di-n-propylamino-3-(4'-chloro-4-biphenylyl)-butane,

1-di-n-propylamino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-diisopropylamino-3-p-biphenylyl-butane,

1-diisopropylamino-3-(4'-fluoro-4-biphenylyl)-butane,

1-diisopropylamino-3-(4'-chloro-4-biphenylyl)-butane,

1-diisopropylamino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-di-n-butylamino-3-p-biphenylyl-butane,

1-di-n-butylamino-3-(4'-fluoro-4-biphenylyl)-butane,

1-di-n-butylamino-3-(4'-chloro-4-biphenylyl)-butane,

1-di-n-butylamino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-diisobutylamino-3-p-biphenylyl-butane,

1-diisobutylamino-3-(4'-fluoro-4-biphenylyl)-butane,

1-diisobutylamino-3-(4'-chloro-4-biphenylyl)-butane,

1-diisobutylamino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-di-n-pentylamino-3p-biphenylyl-butane,

1-di-n-pentylamino-3-(4'-fluoro-4-biphenylyl)-butane,

1-di-n-pentylamino-3-(4'-chloro-4-biphenylyl)-butane,

1-di-n-pentylamino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-di-n-hexylamino-3-p-biphenylyl-butane,

1-di-n-hexylamino-3-(4'-fluoro-4-biphenylyl)-butane,

1-di-n-hexylamino-3-(4'-chloro-4-biphenylyl)-butane,

1-di-n-hexylamino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-(2-dimethylamino-ethylamino)-3-p-biphenylyl-butane,

1-(2-dimethylamino-ethylamino)-3-(4'-fluoro-4-biphenylyl)-butane,

1-(2-dimethylamino-ethylamino)-3-(4'-chloro-4-biphenylyl)-butane,

1-(2-dimethylamino-ethylamino)-3-(4-p-chlorophenoxy-phenyl)-butane,

1-(2-diethylamino-ethylamino)-3-p-biphenylyl-butane,

1-(2-diethylamino-ethylamino)-3-(4'-fluoro-4-biphenylyl)-butane,

1-(2-diethylamino-ethylamino)-3-(4'-chloro-4-biphenylyl)-butane,

1-(2-diethylamino-ethylamino)-3-(4-p-chlorophenoxy-phenyl)-butane,

1-(3-dimethylamino-propylamino)-3-p-biphenylyl-butane,

1-(3-dimethylamino-propylamino)-3-(4'-fluoro-4-biphenylyl)-butane,

1-(3-dimethylamino-propylamino)-3-(4'-chloro-4-biphenylyl)-butane,

1-(3-dimethylamino-propylamino)-3-(4-p-chlorophenoxy-phenyl)-butane,

1-(2-methylpiperidino)-3-p-biphenylyl-butane,

1-(2-methylpiperidino)-3-(4'-fluoro-4-biphenylyl)-butane,

1-(2-methylpiperidino)-3-(4'-chloro-4-biphenylyl)-butane,

1-(2-methylpiperidino)-3-(4-p-chlorophenoxy-phenyl)-butane,

1-(3-methylpiperidino)-3-p-biphenylyl-butane,

1-(3-methylpiperidino)-3-(4'-fluoro-4-biphenylyl)-butane,

1-(3-methylpiperidino)-3-(4'-chloro-4-biphenylyl)-butane,

1-(3-methylpiperidino)-3-(4-p-chlorophenoxy-phenyl)-butane,

1-(2,6-dimethylpiperidino)-3-p-biphenylyl-butane,

1-(2,6-dimethylpiperidino)-3-(4'-fluoro-4-biphenylyl)-butane,

1-(2,6-dimethylpiperidino)-3-(4'-chloro-4-biphenylyl)-butane,

1-(2,6-dimethylpiperidino)-3-(4-p-chlorophenoxy-phenyl)-butane,

1-(4-methyl-piperazino)-3-p-biphenylyl-butane,

1-(4-methyl-piperazino)-3-(4'-fluoro-4-biphenylyl)-butane,

1-(4-methyl-piperazino)-3-(4'-chloro-4-biphenylyl)-butane,

1-(4-methyl-piperazino)-3-(4-p-chlorophenoxy-phenyl)-butane,

1-(4-ethyl-piperazino)-3-p-biphenylyl-butane,

1-(4-ethyl-piperazino)-3-(4'-fluoro-4-biphenylyl)-butane,

1-(4-ethyl-piperazino)-3-(4'-chloro-4-biphenylyl)-butane,

1-(4-ethyl-piperazino)-3-(4-p-chlorophenoxy-phenyl)-butane,

1-(4-n-hexyl-piperazino)-3-p-biphenylyl-butane,

1-(4-n-hexyl-piperazino)-3-(4'-fluoro-4-biphenylyl)-butane,

1-(4-n-hexyl-piperazino)-3-(4'-chloro-4-biphenylyl)-butane,

1-(4-n-hexyl-piperazino)-3-(4-p-chlorophenoxy-phenyl)-butane,

1-[4-(2-hydroxyethyl)-piperazino]-3-p-biphenylyl-butane,

1-[4-(2-hydroxyethyl)-piperazino]-3-(4'-fluoro-4-biphenylyl)-butane,

1-[4-(2-hydroxyethyl)-piperazino]-3-(4'-chloro-4-biphenylyl)-butane and

1-[4-(2-hydroxyethyl)-piperazino]-3-(4-p-chlorophenoxy-phenyl)-butane.

EXAMPLE 49

A solution of 24.1 g of 3-(4'-fluoro-4-biphenylyl)-2-buten-1-yl-amine in500 ml of ethylacetate is hydrogenated, over 10 g of 5% Pd-on-charcoalat 20° and normal pressure until the absorption of hydrogen has ceased.The mixture is filtered and evaporated to give3-(4'-fluoro-4-biphenylyl)-butylamine, hydrochloride, m.p. 222°-224°.

EXAMPLE 50

3.71 g of 1-phthalimido-3-p-biphenylyl-butan-3-ol are dissolved in 20 mlof acetic acid, a solution of 0.8 g of chlorine in 20 ml of acetic acidis added dropwise, while stirring, at 20°, and the mixture is stirredfor a further hour and evaporated.1-Phthalimido-3-(4'-chloro-4-biphenylyl)-butan-3-ol, m.p. 177°-179°, isobtained after working up in the customary manner.

EXAMPLE 51

1-Piperidino-3-(4'-bromo-4-biphenylyl)-butan-3-ol, m.p. 89°-91°, isobtained, analogously to Example 50, from1-piperidino-3-p-biphenylyl-butan-3-ol, using an equivalent quantity ofbromine in acetic acid.

EXAMPLE 52

A solution of 2.25 g of 3-p-biphenylyl-butylamine and 1.5 g ofbenzaldehyde in 25 ml of benzene is boiled for 2 hours under a waterseparator. The solution of the resulting1-benzylidene-amino-3-p-biphenylyl-butane is heated with 5 g ofmethyliodide for 12 hours at 150° in a tube and is then evaporated. Theresulting quaternary salt is boiled for 10 minutes in 90% ethanol. Themixture is evaporated again and taken up in dilute hydrochloric acid andthe benzaldehyde which has been split off is extracted with ether. Theacid aqueous solution is rendered alkaline by means of sodium hydroxidesolution and worked up in the customary manner. This gives1-methylamino-3-p-biphenylyl-butane.

EXAMPLE 53

A mixture of 2.62 g of 3-p-biphenylyl-butylamine hydrochloride, 5 ml offormic acid, 0.7 g of sodium formate and 4 ml of 40% formaldehydesolution is heated to 60° for 3 hours and then to 100° for 12 hours.1-Dimethylamino-3-biphenylyl-butane is obtained after working up in thecustomary manner.

The following are obtained analogously from the corresponding primaryamines:

1-Dimethylamino-3-(2'-fluoro-4-biphenylyl)-butane,

1-dimethylamino-3-(4'-fluoro-4-biphenylyl)-butane,

1-dimethylamino-3-(2'-chloro-4-biphenylyl)-butane,

1-dimethylamino-3-(4'-chloro-4-biphenylyl)-butane,

1-dimethylamino-3-(2'-bromo-4-biphenylyl)-butane,

1-dimethylamino-3-(4'-bromo-4-biphenylyl)-butane,

1-dimethylamino-3-(2',4'-difluoro-4-biphenylyl)-butane,

1-dimethylamino-3-(2',4'-dichloro-4-biphenylyl)-butane,

1-dimethylamino-3-(2',4'-dibromo-4-biphenylyl)-butane,

1-dimethylamino-3-p-phenoxy-phenyl-butane,

1-dimethylamino-3-(4-o-fluorophenoxy-phenyl)-butane,

1-dimethylamino-3-(4-p-fluorophenoxy-phenyl)-butane,

1-dimethylamino-3-(4-o-chlorophenoxy-phenyl)-butane,

1-dimethylamino-3-(4-p-chlorophenoxy-phenyl)-butane,

1-dimethylamino-3-(4-o-bromophenoxy-phenyl)-butane,

1-dimethylamino-3-(4-p-bromophenoxy-phenyl)-butane,

1-dimethylamino-3-[4-(2,4-difluorophenoxy)-phenyl]-butane,

1-dimethylamino-3-[4-(2,4-dichlorophenoxy)-phenyl]-butane and

1-dimethylamino-3-[4-(2,4-dibromophenoxy)-phenyl]-butane.

EXAMPLE 54

A mixture of 2.67 g of 1-isopropylamino-3-p-biphenylylbutane, 12 ml offormic acid and 2 g of 40% formaldehyde solution is heated at 60° for 3hours and then at 100° for 12 hours and is then evaporated.1-(N-Methyl-N-isopropylamino)-3-p-biphenylyl-butane is obtained afterworking up in the customary manner.

EXAMPLE 55

A mixture of 2.25 g of 3-p-biphenylyl-butylamine, 1.38 g of potassiumcarbonate, 2.53 g of 1,5-dibromopentane and 15 ml of n-butanol is boiledfor 24 hours, while stirring. The mixture is filtered and the filtrateis evaporated and worked up in the customary manner to give1-piperidino-3-p-biphenylyl-butane.

EXAMPLE 56

A mixture of 2.25 g of 3-p-biphenylyl-butylamine, 20 ml of benzene, 1 mlof pyridine and 1 ml of acetic anhydride is stirred for 3 hours at 25°.1-Acetamido-3-p-biphenylylbutane is obtained after working up in thecustomary manner.

The following are obtained analogously by acetylating the correspondingprimary or secondary amines:

1-Acetamido-3-(2'-fluoro-4-biphenylyl)-butane,

1-acetamido-3-(4'-fluoro-4-biphenylyl)-butane,

1-acetamido-3-(2'-chloro-4-biphenylyl)-butane,

1-acetamido-3-(4'-chloro-4-biphenylyl)-butane, m.p. 118° - 120°,

1-acetamido-3-(2'-bromo-4-biphenylyl)-butane,

1-acetamido-3-(4'-bromo-4-biphenylyl)-butane,

1-acetamido-3-(2',4'-difluoro-4-biphenylyl)-butane,

1-acetamido-3-(2',4'-dichloro-4-biphenylyl)-butane,

1-acetamido-3-(2',4'-dibromo-4-biphenylyl)-butane,

1-acetamido-3-p-phenoxy-phenyl-butane,

1-acetamido-3-(4-o-fluorophenoxy-phenyl)-butane,

1-acetamido-3-(4-p-fluorophenoxy-phenyl)-butane,

1-acetamido-3-(4-o-chlorophenoxy-phenyl)-butane,

1-acetamido-3-(4-p-chlorophenoxy-phenyl)-butane,

1-acetamido-3-(4-o-bromophenoxy-phenyl)-butane,

1-acetamido-3-(4-p-bromophenoxy-phenyl)-butane,

1-acetamido-3-[4-(2,4-difluorophenoxy)-phenyl]-butane,

1-acetamido-3-[4-(2,4-dichlorophenoxy)-phenyl]-butane,

1-acetamido-3-[4-(2,4-dibromophenoxy)-phenyl]-butane,

1-acetamido-3-p-biphenylyl-3-butanol,

1-acetamido-3-(2'-fluoro-4-biphenylyl)-3-butanol,

1-acetamido-3-(4'-fluoro-4-biphenylyl)-3-butanol,

1-acetamido-3-(2'-chloro-4-biphenylyl)-3-butanol,

1-acetamido-3-(4'-chloro-4-biphenylyl)-3-butanol,

1-acetamido-3-(2'-bromo-4-biphenylyl)-3-butanol,

1-acetamido-3-(4'-bromo-4-biphenylyl)-3-butanol,

1-acetamido-3-(2',4'-difluoro-4-biphenylyl)-3-butanol,

1-acetamido-3-(2',4'-dichloro-4-biphenylyl)-3-butanol,

1-acetamido-3-(2',4'-dibromo-4-biphenylyl)-3-butanol,

1-acetamido-3-p-phenoxy-phenyl-3-butanol,

1-acetamido-3-(4-o-fluorophenoxy-phenyl)-3-butanol,

1-acetamido-3-(4-p-fluorophenoxy-phenyl)-3-butanol,

1-acetamido-3-(4-o-chlorophenoxy-phenyl)-3-butanol,

1-acetamido-3-(4-p-chlorophenoxy-phenyl)-3-butanol,

1-acetamido-3-(4-o-bromophenoxy-phenyl)-3-butanol,

1-acetamido-3-(4-p-bromophenoxy-phenyl)-3-butanol,

1-acetamido-3-[4-(2,4-difluorophenoxy)-phenyl]-3-butanol,

1-acetamido-3-[4-(2,4-dichlorophenoxy)-phenyl]-3-butanol,

1-acetamido-3-[4-(2,4-dibromophenoxy)-phenyl]-3-butanol and

1-(N-methyl-acetamido)-3-p-biphenylyl-butan-3-ol.

EXAMPLE 57

A mixture of 2.6 g of 3-(4'-chloro-4-biphenylyl)-butylamine, 12 ml ofpyridine and 1 ml of acetyl chloride is allowed to stand for 2 hours,decomposed with water and worked up in the customary manner to give

1-acetamido-3-(4'-chloro-4-biphenylyl)-butane, m.p. 118°- 120°.

The following are obtained analogously by acylating the correspondingprimary or secondary amines:

1-Propionamido-3-p-biphenylyl-butane,

1-propionamido-3-(4'-fluoro-4-biphenylyl)-butane,

1-propionamido-3-(4'-chloro-4-biphenylyl)-butane,

1-propionamido-3-(4-p-chlorophenoxy-phenyl)-butane,

1-butyramido-3-p-biphenylyl-butane,

1-butyramido-3-(4'-fluoro-4-biphenylyl)-butane,

1-butyramido-3-(4'-chloro-4-biphenylyl)-butane,

1-butyramido-3-(4-p-chlorophenoxy-phenyl)-butane,

1-isobutyramido-3-p-biphenylyl-butane,

1-isobutyramido-3-(4'-fluoro-4-biphenylyl)-butane,

1-isobutyramido-3-(4'-chloro-4-biphenylyl)-butane,1-isobutyramido-3-(4-p-chlorophenoxy-phenyl)-butane,

1-propionamido-3-p-biphenylyl-butan-3-ol,

1-propionamido-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-propionamido-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-propionamido-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-butyramido-3-p-biphenylyl-butan-3-ol,

1-butyramido-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-butyramido-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-butyramido-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-isobutyramido-3-p-biphenylyl-butan-3-ol,

1-isobutyramido-3-(4'-fluoro-4-biphenylyl)-butan-3-ol,

1-isobutyramido-3-(4'-chloro-4-biphenylyl)-butan-3-ol,

1-isobutyramido-3-(4-p-chlorophenoxy-phenyl)-butan-3-ol,

1-(N-methyl-propionamido)-3-p-biphenylyl-butan-3-ol,

1-valeramido-3-p-biphenylyl-butan-3-ol and

1-caproamido-3-p-biphenylyl-butan-3-ol.

EXAMPLE 58

2.25 g of 3-p-biphenylyl-butylamine and 5 g of phthalic anhydride areheated at 120°for 90 minutes, cooled and worked up in the customarymanner to give 1-phthalimido-3-p-biphenylyl-butane, m.p. 120°- 123°.

EXAMPLE 59

A solution of 28.5 g of 1-acetamido-3-(4'-fluoro-4-biphenylyl)-butane in800 ml of 10% methanolic KOH solution is boiled for 48 hours. Thesolution is concentrated and worked up using water and ether to give3-(4'-fluoro-4-biphenylyl)-butylamine; hydrochloride, m.p. 222° - 224°.

EXAMPLE 60

37.3 g of 1-phthalimido-3-(4'-fluoro-4-biphenylyl)- butane are boiledfor 6 hours with 400 ml of 20% aqueous hydrochloric acid, evaporated andworked up using sodium hydroxide solution and ether to give3-(4'-fluoro-4-biphenylyl)-butylamine, hydrochloride, m.p. 222°- 224°.

EXAMPLE 61

A solution of 3.55 g of 1-phthalimido-3-p-biphenylylbutane and 1.25 mlof 80% hydrazine hydrate in 40 ml of methanol is boiled for 4 hours.1-(3,4-Dihydro-4-oxo-1-phthalazinyl-amino)-3-p-biphenylyl-butane isprecipitated by adding water.

The following are obtained analogously by hydrazinolysis of thecorresponding phthalimides:

1-(3,4-Dihydro-4-oxo-1-phthalazinyl-amino)-3-(2'-fluoro-4-biphenylyl)-butane,

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-(4'-fluoro-4-biphenylyl)-butane,m.p. 150 - 168°,

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-(2'-chloro-4-biphenylyl)-butane,

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-(4'-chloro-4-biphenylyl)-butane,m.p. 195°,

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-(2'-bromo-4-biphenylyl)-butane

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-(4'-bromo-4-biphenylyl)-butane

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-(2',4'-difluoro-4-biphenylyl)-butane,

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3(2',4'-dichloro-4-biphenylyl)-butane,

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-(2',4'-dibromo-4-biphenylyl)-butane,

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-p-phenoxy-phenyl-butane,

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-(4-o-fluorophenoxy-phenyl)-butane,

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-(4-p-fluorophenoxy-phenyl)-butane,

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-(4-o-chlorophenoxy-phenyl)-butane,

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-(4-p-chlorophenoxy-phenyl)-butane,

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-(4-o-bromophenoxy-phenyl)-butane,

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-(4-p-bromophenoxy-phenyl)-butane,

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-[4-(2,4-difluorophenoxy)-phenyl]-butane,

1-(3,4-dihydrp-4-oxo-1-phthalazinyl-amino)=3-[4-(2,4-dichlorophenoxy)-phenyl]-butaneand

1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-[4-(2,4-dibromophenoxy)-phenyl]-butane.

EXAMPLe 62

38.95 g of 1-phthalimido-3-(4'-chloro-4-biphenylyl)-butane are boiledwith 12.2 ml of 80% hydrazine hydrate in 400 ml of ethanol for 2 hours,while stirring, water is added, the mixture is cooled and the resulting1-(3,4-dihydro-4-oxo-1-phthalazinyl-amino)-3-(4'-chloro-4-biphenylyl)-butane(m.p. 195°) is filtered off, dissolved in 450 ml of ethanol and 450 mlof 37% hydrochloric acid and boiled for 30 minutes, while stirring. Thesolution is concentrated and worked up using sodium hydroxide solutionand ethyl acetate to give 3-(4'-chloro-4-biphenylyl)-butylamine.Hydrochloride, m.p. 256°-259°.

EXAMPLE 63

(a) 1-Ethylamino-3-(4°-chloro-4-biphenylyl)-butane is obtained,analogously to Example 1, from1-acetamido-3-(4'-chloro-4-biphenylyl)-butane and LiAlH₄.

(b) 1-Ethylamino-3-(4'-chloro-4-biphenylyl)-butane is acetaylated,analogously to Example 26, to give1-(N-ethylacetamido)-3-(4'-chloro-4-biphenylyl)-butane.

(c) 1-(N-Ethyl-acetamido)-3-(4'-chloro-4-biphenylyl)-butane is reduced,analogously to Example 1, employing LiAlH₄ to give1-diethylamino-3-(4'-chloro-4-biphenyl)-butane, m.p. 42° - 44°.

EXAMPLE 64

A mixture of 2.82 g of 1-acetamido-3-p-biphenylyl-butan-3-ol, 0.1 g ofp-toluenesulfonic acid and 70 ml of toluene is boiled for 2 hours undera water separator, 1-Acetamido-3-p-biphenylyl-2-butene is obtained afterworking up in the customary manner.

The following are obtained analogously by dehydrating the correspondingalcohols:

1-Acetamido-3-(2'-fluoro-4-biphenylyl)-2-butene,

1-acetamido-3-(4'-fluoro-4-biphenylyl)-2-butene, m.p. 174- 176°,

1-acetamido-3-(2'-chloro-4-biphenylyl)-2-butene,

1-acetamido-3-(4'-chloro-4-biphenylyl)-2-butene,

1-acetamido-3-(2'-bromo-4-biphenylyl)-2-butene,

1-acetamido-3-(4'-bromo-4-biphenylyl)-2-butene,

1-acetamido-3-(2',4'-difluoro-4-biphenylyl)-2-butene,

1-acetamido-3-(2',4'-dichloro-4-diphenylyl)-2-butene,

1-acetamido-3-(2',4'-dibromo-4-biphenylyl)-2-butene,

1-acetamido-3-p-phenoxy-phenyl-2-butene,

1-acetamido-3-(4-o-fluorophenoxy-phenyl)-2-butene,

1-acetamido-3-(4-p-fluorophenoxy-phenyl)-2-butene,

1-acetamido-3-(4-o-chlorophenoxy-phenyl)-2-butene,

1-acetamido-3-(4-p-chlorophenoxy-phenyl)-2-butene,

1-acetamido-3-(4-o-bromophenoxy-phenyl)-2-butene,

1-acetamido-3-(4-p-bromophenoxy-phenyl)-2-butene,

1-acetamido-3-[4-(2,4-difluorophenoxy)-phenyl]-2-butene,

1-acetamido-3-[4-(2,4-dichlorophenoxy)-phenyl]-2-butene and

1-acetamido-3-[4-(2,4-dibromophenoxy)-phenyl]-2-butene.

EXAMPLE 65

2.25 g of 3-p-biphenylyl-butylamine are dissolved in 30 ml of formicacid, 10 ml of acetic anhydride are added dropwise at 60°, whilestirring, and the mixture is allowed to stand overnight and worked up inthe customary manner to give 1-formamido-3-p-biphenylyl-butane.

The examples which follow relate to pharmaceutical preparations whichcontain amines of Formula I or their acid addition salt.

EXAMPLE A: Tablets

A mixture of 1 kg of 3-(4'-chloro-4-biphenylyl)-butylamine tartrate, 4kg of lactose, 1.2 kg of potato starch, 0.2 kg of talc and 0.1 kg ofmagnesium stearate is pressed into tablets in the customary manner, insuch a way that each tablet contains 100 mg of active compound.

EXAMPLE B: Dragees

Tablets are pressed analogously to Example A, and are then coated in thecustomary manner with a coating of sucrose, potato starch, talc,tragacanth and colorant.

EXAMPLE C: Capsules

5 kg of 3-(4'-fluoro-4-biphenylyl)-butylamine hydrochloride are filledinto hard gelatine capsules in the customary manner, in such a way thateach capsule contains 250 mg of the active compound.

Tablets, dragees and capsules which contain one or more of the remainingactive compounds of Formula I and/or their physiologically acceptableacid addition salts, can be obtained analogously.

The preceding examples can be repeated with similar success bysubstituting the generically or specifically described reactants and/oroperating conditions of this invention for those used in the precedingexamples.

From the foregoing description, one skilled in the art can easilyascertain the essential characteristics of this invention, and withoutdeparting from the spirit and scope thereof, can make various changesand modifications of the invention to adapt it to various usages andconditions.

What is claimed is:
 1. An araliphatic nitrogen compound of the formula

     R--C(OH) (CH.sub.3)--CH.sub.2 --(CH.sub.2).sub.n -Z

wherein R is 4-biphenylyl monosubstituted or polysubstituted by F, Cland/or Br; Z is --NR¹ R², R¹ and R² each are H or alkyl of 1-6 carbonatoms, or, collectively, are alkylene of 4-7 carbon atoms; and n is 0, 1or 2, and their physiologically acceptable acid addition salts.
 2. Acompound of claim 1 wherein Z is piperidino.
 3. A compound of claim 1wherein A is - C(OH)(CH₃)CH₂ CH₂.
 4. A compound of claim 1 wherein Z isamino.
 5. A compound of claim 1 wherein Z is pyrrolidino.
 6. A compoundof claim 1 wherein Z is dialkylamino.
 7. A compound of claim 1 wherein Zis monoalkylamino.
 8. A compound of claim 1,1-piperidino-3-(4'-fluoro-4-biphenylyl)-butan-3-ol or a physiologicallyacceptable acid addition salt thereof.
 9. A compound of claim 1,3-(2'-fluoro-4-biphenylyl)-3-hydroxy-butylamine or a physiologicallyacceptable salt thereof.
 10. A compound of claim 1,3-(4'-fluoro-4-biphenylyl)-3-hydroxy-butylamine or a physiologicallyacceptable salt thereof.
 11. A compound of claim 1,3-(4'-chloro-4-biphenylyl)-3-hydroxy-butylamine or a physiologicallyacceptable salt thereof.
 12. A compound of claim 1,3-(2',4'-difluoro-4-biphenylyl)-3-hydroxy-butylamine or aphysicologically acceptable salt thereof.
 13. A compound of claim 1,1-piperidino-3-(4'-bromo-4-biphenylyl)-butan-3-ol or a physiologicallyacceptable salt thereof.
 14. A pharmaceutical composition comprising inunit dosage form, an anti-inflammatorily effective amount per unitdosage of a compound of claim 1 in admixture with a pharmaceuticallyacceptable carrier.
 15. A method of treating inflammatory conditionswhich comprises administering systemically to the affected patient ananti-inflammatorily effective amount of a compound of claim
 1. 16.3-p-Biphenylyl-3-hydroxy-butylamine or a physiologically acceptable saltthereof.
 17. 1-Piperidino-3-p-biphenylyl-butan-3-ol or a physiologicallyacceptable salt thereof.